APPETITE STIMULANT & Cannabis studies completed


Usually hunger enhancement is considered an undesirable side effect of certain drugs as it leads to unwanted weight gain, but sometimes it can be beneficial and cannabis may be prescribed solely for this purpose, especially when the patient is suffering from severe hunger loss or muscle wasting due to cystic fibrosis, anorexia, old age, cancer or AIDS.

There are several medications including cannabis, which can cause a boost in hunger. Tricyclic antidepressants (TCAs), tetracyclic antidepressants, natural or synthetic cannabinoids, first-generation antihistamines, most antipsychotics and many steroid hormones. source wikipedia

Science & Research

2018 - Study ~ Hunger, ghrelin and the gut.

Science Direct: Brain Research.

2018 - Abstract ~ Salivary endocannabinoids and N-acylethanolamines upon mastication of a semisolid food: implications in fat taste, appetite and food liking.

Journal of Food & Function.

2017 - Study ~ Role of Endocannabinoids on Sweet Taste Perception, Food Preference, and Obesity related Disorders.

Oxford Academic: Chemical Senses.

2017 - Abstract ~ Are cannabinoids an alternative for cachexia-anorexia syndrome in patients with advanced cancer?


2017 - Abstract ~ Cannabinoids for the treatment of neuropsychiatric symptoms, pain and weight loss in dementia.
Current Opinion in Psychiatry.

2017 - Abstract ~ Anorexigenic effects induced by RVD-hemopressin(α) administration.

Pharmacological Reports.

2017 - Abstract ~ A behavioral and pharmacological characterization of palatable diet alternation in mice.

Pharmacology Biochemistry and Behavior.

2017 - Abstract ~ Consequence of dopamine D2 receptor blockade on the hyperphagic effect induced by cannabinoid CB1 and CB2 receptors in layers.

British Poultry Science.

2017 - Abstract ~ 2-Arachidonoylglycerol as a possible treatment for anorexia nervosa in animal model in mice.

Brain Research Journal.

2017 - Abstract ~ Endocannabinoid-dependent disinhibition of orexinergic neurons: Electrophysiological evidence in leptin-knockout obese mice.

Molecular Metabolism.

2017 - Abstract ~ Endocannabinoid modulation of homeostatic and non-homeostatic feeding circuits.

Science Direct: Neuropharmacology Journal.

2017 - Abstract ~ Effects of anandamide administration on components of reward processing during free choice.

Pharmacology Biochemistry and Behavior.

2017 - Abstract ~ The rewarding effects of ethanol are modulated by binge eating of a high-fat diet during adolescence.

Science Direct: Neuropharmacology Journal.

2017 - Abstract ~ Cannabinoids activate monoaminergic signaling to modulate key C. elegans behaviors.

JNeurosci: The Journal of Neuroscience.

2017 - Abstract ~ A cannabigerol-rich Cannabis sativa extract, devoid of [INCREMENT]9- tetrahydrocannabinol, elicits hyperphagia in rats.

Behavioral Pharmacology Journal.

2017 - Abstract ~ Peripheral endocannabinoid signaling controls hyperphagia in western diet-induced obesity.

Science Direct: Physiology & Behavior Journal.

2017 - Study ~ Central and peripheral control of food intake.

Endocrine Regulations Journal.

2017 - Study ~ A cannabinoid receptor antagonist attenuates ghrelin-induced activation of the mesolimbic dopamine system in mice.

Science Direct: Physiology & Behavior Journal.

2017 - Study ~ Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity.

Nature Publishing: Scientific Reports.

2017 - Study ~ Pharmacological inhibition of cannabinoid receptor 1 stimulates gastric release of nesfatin-1 via the mTOR pathway.

World Journal of Gastroenterology.

2017 - Study ~ Hedonic eating in Prader-Willi syndrome is associated with blunted PYY secretion.

Food & Nutrition Journal.

2017 - Study ~ Cannabinoid Receptor Signaling in Central Regulation of Feeding Behavior: A MiniReview.

Frontiers in Neuroscience.

2017 - Study ~ Oral Administration of the Endocannabinoid Anandamide during Lactation: Effects on Hypothalamic Cannabinoid Type 1 Receptor and Food Intake in Adult Mice.

Journal of Nutrition and Metabolism.

2017 - Study ~ Inhibiting parabrachial fatty acid amide hydrolase activity selectively increases the intake of palatable food via cannabinoid CB1 receptors.

American Journal of Physiology.

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2014 - Study ~ Dronabinol in severe, enduring anorexia nervosa: A randomized controlled trial

2014 - Study ~ Rimonabant's reductive effects on high densities of food reinforcement, but not
palatability, in lean and obese Zucker rats.

2014 - Study ~ Cannabinoid type-1 Receptors in The Paraventricular Nucleus of The Hypothalamus Inhibit Stimulated Food Intake.

2014 - Study ~ The endocannabinoid system controls food intake via olfactory processes

2014 - Study ~ Effect of intermittent cold exposure on brown fat activation, obesity, and energy homeostasis in mice.

2013 - Study ~ Ghrelin-Induced Orexigenic Effect in Rats Depends on the Metabolic Status and Is Counteracted by Peripheral CB1 Receptor Antagonism.

2013 - Study ~ Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons

2013 - Study ~ Hypothalamic 2-Arachidonoylglycerol Regulates Multistage Process of High-Fat Diet Preferences

2013 - Study ~ Brain Molecules and Appetite: The Case of Oleoylethanolamide

2013 - Study ~ Effect of Diet on Tissue Levels of Palmitoylethanolamide

2013 - Study ~ Reduced Food Intake is the Major Contributor to the Protective Effect of Rimonabant on Islet in Established Obesity-Associated Type 2 Diabetes.

2013 - Study ~ The Gastric CB1 Receptor Modulates Ghrelin Production through the mTOR Pathway to Regulate Food Intake.

2013 - Study ~ Orexin neurons use endocannabinoids to break obesity-induced inhibition

2013 - Study ~ Developmental Role for Endocannabinoid Signaling in Regulating Glucose Metabolism and Growth.

2013 - Study ~ Effects of glucagon-like peptide-1 receptor stimulation and blockade on food
consumption and body weight in rats treated with a cannabinoid CB1 receptor agonist
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2013 - Study ~ Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids

2013 - Study ~ Cannabis and Δ(9)-tetrahydrocannabinol (THC) for weight loss?

2013 - Study ~ Taste sensitivity to 6-n-propylthiouracil is associated with endocannabinoid plasma levels in normal-weight individuals.

2013 - Study ~ Novel antiobesity agents: Synthesis and pharmacological evaluation of analogues of Rimonabant and of LH21.

2013 - Study ~ Endocannabinoid signaling in the gut mediates preference for dietary unsaturated fats.

2013 - Study ~ AM404 attenuates reinstatement of nicotine seeking induced by nicotine-associated cues and nicotine priming but does not affect nicotine- and food-taking.

2013 - Study ~ Endocannabinoid signaling in the gut mediates preference for dietary unsaturated fats.

2013 - Study ~ Long-term CB1 receptor blockade enhances vulnerability to anxiogenic-like effects of cannabinoids.

2013 - Study ~ Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade.

2013 - Study ~ Fat to treat fat: Emerging relationship between dietary PUFA, endocannabinoids, and obesity.

2013 - Study ~ Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade.

2013 - Study ~ Central functional response to the novel peptide cannabinoid, hemopressin.

2013 - Study ~ The inverse agonist of CB1 receptor SR141716 blocks compulsive eating of palatable food.

2013 - Study ~ Cannabinoid receptors and cholecystokinin in feeding inhibition.

2013 - Study ~ The endocannabinoid system in obesity

2013 - Study ~ Rimonabant precipitates anxiety in rats withdrawn from palatable food: role of the central amygdale.

2013 - Study ~ The satiety signal oleoylethanolamide stimulates oxytocin neurosecretion from rat hypothalamic neurons.

2013 - Study ~ The Role of the Endocannabinoid System in Eating Disorders: Neurochemical and Behavioural Preclinical Evidence.

2013 - Study ~ Therapeutic potential of cannabinoid medicines.

2013 - Study ~ Food for thought: hormonal, experiential, and neural influences on feeding and obesity.

2013 - Study ~ Cannabis withdrawal syndrome: An important diagnostic consideration in adolescents presenting with disordered eating.

2013 - Study ~ The regulation of food intake by the gut-brain axis: implications for obesity

2013 - Study ~ Cannabinoids, eating behaviour, and energy homeostasis.

2013 - Study ~ Concurrent pharmacological modification of cannabinoid-1 and glucagon-like peptide-1 receptor activity affects feeding behavior and body weight in rats fed a free-choice, high- carbohydrate diet.

2013 - Study ~ The regulation of food intake by the gut-brain axis: implications for obesity

2013 - Study ~ Cannabinoids, eating behaviour, and energy homeostasis.

2013 - Study ~ Concurrent pharmacological modification of cannabinoid-1 and glucagon-like peptide-1 receptor activity affects feeding behavior and body weight in rats fed a free-choice, high-carbohydrate diet.

2013 - News ~ Key Shift in Brain That Creates Drive to Overeat Identified

2013 - News ~ Study: Why Pot Smokers Are Skinnier

2013 - News ~ Too little sleep may trigger the 'munchies' by raising levels of an appetite-controlling molecule

2013 - News ~ Too little sleep may trigger the 'munchies' by raising levels of an appetite-controlling molecule

2012 - Study ~ Hypothalamic 2-arachidonoylglycerol regulates multistage process of high-fat diet preferences.

2012 - Study ~ Contrasting effects of different cannabinoid receptor ligands on mouse ingestive behavior.

2012 - Study ~ Noladin ether, a putative endocannabinoid, enhances motivation to eat after acute systemic administration in rats.

2012 - Study ~ Effects of the anandamide uptake blocker AM404 on food intake depend on feeding status and route of administration.

2012 - Study ~ Rimonabant eliminates responsiveness to workload changes in a time-constrained food-reinforced progressive ratio procedure in rats.

2012 - Study ~ Cannabinol and cannabidiol exert opposing effects on rat feeding patterns.

2012 - Study ~ The potential use of cannabidiol in the therapy of metabolic syndrome.

2012 - Study ~ The thrifty lipids: endocannabinoids and the neural control of energy conservation.

2012 - Study ~ Stimulation of acumbens shell cannabinoid CB(1) receptors by noladin ether, a putative endocannabinoid, modulates food intake and dietary selection in rats.

2012 - Study ~ Photoperiodic Changes in Endocannabinoid Levels and Energetic Responses to Altered Signalling at CB1 Receptors in Siberian Hamsters.

2012 - Study ~ The role of the endocannabinoid system in eating disorders: pharmacological implications.

2012 - Study ~ Hypothalamic CB1 Cannabinoid Receptors Regulate Energy Balance in Mice.

2012 - Study ~ 2-Arachidonoylglycerol Signaling in Forebrain Regulates Systemic Energy Metabolism.

2012 - Study ~ GPR119 as a fat sensor.

2012 - Study ~ Non-Δ⁹tetrahydrocannabinol phytocannabinoids stimulate feeding in rats.

2012 - Study ~ Structural analogs of pyrazole and sulfonamide cannabinoids: Effects on acute food intake in mice.

2012 - Study ~ Cannabinoid Type 1 Receptor Gene Polymorphism and Macronutrient Intake.

2012 - Study ~ The therapeutic potential of cannabis and cannabinoids.

2012 - Study ~ Simultaneous postprandial deregulation of the orexigenic endocannabinoid anandamide and the anorexigenic peptide YY in obesity

2012 - Study ~ Pharmacological modulation of the endocannabinoid signalling alters binge-type eating behaviour in female rats

2012 - News ~ Cannabis as Painkiller

2011 - Study ~ Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial.

2011 - Study ~ Cannabidiol inhibits the hyperphagia induced by cannabinoid-1 or serotonin-1A receptor agonists.

2011 - Study ~ Cannabidiol decreases body weight gain in rats: Involvement of CB2 receptors.

2011 - Study ~ Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation.

2011 - Study ~ The neutral cannabinoid CB₁ receptor antagonist AM4113 regulates body weight through changes in energy intake in the rat.

2011 - Study ~ Cannabidiol potentiates Δ(9)-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats.

2011 - Study ~ Fish oil promotes survival and protects against cognitive decline in severely undernourished mice by normalizing satiety signals.

2011 - Study ~ Non-Δ9tetrahydrocannabinol phytocannabinoids stimulate feeding in rats.

2011 - Study ~ Increment of hypothalamic 2-arachidonoylglycerol induces the preference for a high-fat diet via activation of cannabinoid 1 receptors.

2011 - Study ~ Cannabinoids in children.

2011 - Study ~ Gut fat sensing in the negative feedback control of energy balance--recent advances.

2011 - News ~ Science: Cannabis influences blood levels of appetite hormones in people with HIV.

2011 - News ~ Ingredient in cannabis restores taste for cancer patients.

2011 - News ~ Cannabis Ingredient Can Help Cancer Patients Regain Their Appetites and Sense of Taste, Study Finds.

2011- News ~ How Does Marijuana Help Cancer Patients?

2011 - News ~ Study helps explain why fatty foods are complicit in weight gain.

2011 - News ~ Binge Eating May Be a High All Its Own.

2011 - News ~ Body's natural marijuana-like chemicals make fatty foods hard to resist.

2011 - News ~ Endocannabinoid Signaling In Dietary Restriction And Lifespan Extension.

2011 - News ~ Smoking marijuana not linked to obesity: study.

2011 - Anecdotal ~ Father: Medical marijuana eased pain of my cancer-battling son.

2010 - Study ~ The fat-induced satiety factor oleoylethanolamide suppresses feeding through central release of oxytocin.

2010 - Study ~ The multiple functions of the endocannabinoid system: a focus on the regulation of food intake.

2010 - Study ~ Expression of cannabinoid CB1 receptors by vagal afferent neurons: kinetics and role in influencing neurochemical phenotype.

2010 - Study ~ CD36 gene deletion decreases oleoylethanolamide levels in small intestine of free-feeding mice.

2010 - Study ~ Cannabis constituents modulate δ9-tetrahydrocannabinol-induced hyperphagia in rats.

2010 - Study ~ A nonsynonymous polymorphism in cannabinoid CB2 receptor gene is associated with eating disorders in humans and food intake is modified in mice by its ligands.

2010 - Study ~ Cannabidiol Attenuates the Appetitive Effects of Δ9-Tetrahydrocannabinol in Humans Smoking Their Chosen Cannabis.

2010 - Study ~ Oleoylethanolamide affects food intake and sleep-waking cycle through a hypothalamic modulation.

2010 - Study ~ PP-014 Control of receptor expression in vagal afferent neurons by activation of cannabinoid 1 receptors.

2010 - Study ~ Bimodal control of stimulated food intake by the endocannabinoid system.

2010 - Study ~ Anandamide and AM251, via water, modulate food intake at central and peripheral level in fish.

2010 - Study ~ Analysis of gene expression pattern reveals potential targets of dietary oleoylethanolamide in reducing body fat gain in C3H mice.

2010 - Study ~ A low-Δ9tetrahydrocannabinol cannabis extract induces hyperphagia in rats.

2010 - Study ~ Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age.

2010 - Study ~ The endocannabinoid system modulates the valence of the emotion associated to food ingestion.

2010 - Study ~ Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study.

2010 - News ~ Endocannabinoid Modulation Of Tongue Sweet Taste Receptors May Help Control Feeding Behavior.

2009 - Study ~ Endocannabinoids selectively enhance sweet taste.

2009 - Study ~ Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice.

2009 - Study ~ GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell.

2009 - Study ~ Endocannabinoids and Their Receptors as Targets for Obesity Therapy.

2009 - Study ~ Bidirectional regulation of novelty-induced behavioral inhibition by the endocannabinoid system.

2009 - Study ~ Endogenous cannabinoid signalling and energy balance.

2009 - Study ~ N-acylethanolamines, anandamide and food intake.

2009 - Study ~ Cannabinoids and appetite: food craving and food pleasure.

2009 - Study ~ Effects of cannabinoid drugs on the reinforcing properties of food in gestationally undernourished rats.

2009 - Study ~ Role of cannabinoid CB1 receptors on macronutrient selection and satiety in rats.

2009 - News - Natural Pot-Like Compound Could Fight Obesity.

2009 - News ~ Enhanced Sweet Taste: Endocannabinoids Act Directly on Tongue Taste Receptors.

2009 - News ~ Chemicals in pot stimulate tongue receptors to taste sweetness.

2009 - News ~ Enhanced sweet taste: This is your tongue on pot.

2008 - Study ~ Cannabinoids enhance gastric X/A-like cells activity.

2008 - Study ~ The lipid messenger OEA links dietary fat intake to satiety.

2008 - Study ~ Targeted enhancement of oleoylethanolamide production in proximal small intestine induces across-meal satiety in rats.

2008 - Study ~ Feeding induced by cannabinoids is mediated independently of the melanocortin system.

2008 - Study ~ Activating Parabrachial Cannabinoid CB1 Receptors Selectively Stimulates Feeding of Palatable Foods in Rats.

2008 - Study ~ Endocannabinoids and the Control of Energy Homeostasis.

2008 - Study ~ The role of endocannabinoids in the regulation of gastric emptying: alterations in mice fed a high-fat diet.

2008 - Study ~ Endocannabinoids and the neurochemistry of gluttony.

2008 - Study ~ Biological functions and metabolism of oleoylethanolamide.

2008 - Study ~ Inhibitory effect of the anorexic compound oleoylethanolamide on gastric emptying in control and overweight mice.

2008 - Study ~ Behavioral effects of CB2 cannabinoid receptor activation and its influence on food and alcohol consumption.

2008 - Study ~ Role of endocannabinoids and their analogues in obesity and eating disorders.

2007 - Study ~ The endogenous cannabinoid system: a new player in the brain-gut-adipose axis.

2007 - Study ~ Cannabinol induced hyperphagia: correlation with inhibition of proopiomelaanocortin neutrons.

2007 - Study ~ Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances 'liking' of a sweet reward.

2007 - Study - Dronabinol an effective appetite stimulant.

2007 - Study ~ Pharmacological enhancement of the endocannabinoid system in the nucleus accumbens shell stimulates food intake and increases c-Fos expression in the hypothalamus.

2007 - Study - THC improves appetite and reverses weight loss in AIDS patients.

2007 - Study - Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting.

2007 - Study - Dronabinol and marijuana in HIV-positive marijuana smokers: caloric intake, mood, and sleep.

2007 - Study ~ Anorexia of aging in long term care: is dronabinol an effective appetite stimulant? A pilot study.

2006 - Study - Cancer related anorexia cachexia syndrome.

2006 - Study - The synthetic cannabinoid nabilone improves pain and symptom management in cancer patients.

2006 - Study -Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases.

2006 - Study ~ Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group.

2006 - Study ~ Lack of tolerance to the suppressing effect of rimonabant on chocolate intake in rats.

2006 - Study ~ Effect of a cannabinoid agonist on gastrointestinal transit and postprandial satiation in healthy human subjects: a randomized, placebo-controlled study.

2006 - Study ~ Methods evaluating cannabinoid and endocannabinoid effects on gastrointestinal functions.

2005 - Study ~ Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood.

2005 - Study ~ Food for thought: endocannabinoid modulation of lipogenesis.

2005 - Study ~ Endocannabinoids in the Regulation of Appetite and Body Weight.

2005 - Study ~ Cannabinoids augment the release of neuropeptide Y in the rat hypothalamus.

2005 - Study ~ Effects of the endocannabinoid noladin ether on body weight, food consumption, locomotor activity, and cognitive index in mice.

2005 - News - THC effective in appetite and weight loss in severe lung disease (COPD).

2005 - News - Machinery Of The 'Marijuana Munchies'.

2004 - Study ~ Endocannabinoids: Getting the message across.

2004 - Study ~ Very low doses of delta 8-THC increase food consumption and alter neurotransmitter levels following weight loss.

2004 - Study ~ Overeating, Alcohol and Sucrose Consumption Decrease in Cb1 Receptor Deleted Mice.

2003 - Study - Safety and efficacy of dronabinol in the treatment of agitation in patients with Alzheimer's disease.

2003 - Study ~ The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis.

2003 - Study ~ Endogenous cannabinoid system as a modulator of food intake.

2003 - Study ~ The cannabinoid system: a role in both the homeostatic and hedonic control of eating?

2003 - Study ~ Short-term fasting and prolonged semistarvation have opposite effects on 2-AG levels in mouse brain.

2003 - Study ~ Milk intake and survival in newborn cannabinoid CB1 receptor knockout mice: evidence for a "CB3" receptor.

2002 - Study ~ A Peripheral Mechanism for CB1 Cannabinoid Receptor-Dependent Modulation of Feeding.

2002 - Study ~ Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol.

2001 - Study - Therapeutic Aspects of Cannabis and Cannabinoids.

2001 - Study ~ Dietary intake and nutritional status of US adult marijuana users: results from the Third National Health and Nutrition Examination Survey.

2001 - Study ~ Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats.

2001 - Study ~ Neuroprotection by Delta 9-Tetrahydrocannabinol, the Main Active Compound in Marijuana, against Ouabain-Induced In Vivo Excitotoxicity.

2001 - Letter ~ Leptin-regulated endocannabinoids are involved in maintaining food intake.

2001 - News ~ Attack of the munchies.

2001 - News ~ Scientists crack 'munchies' mystery.

2000 - Study - Immunoactive cannabinoids: Therapeutic prospects for marijuana constituents.

2000 - Study ~ Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice.

2000 - Study ~ Endogenous cannabinoids and appetite.

1997 - Study - The perceived effects of smoked cannabis on patients with multiple sclerosis.

1997 - Study - Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease.

1995 - Study - Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS.

1994 - Study - Delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia.

1994 - Study - Cannabinoids and appetite stimulation.

1993 - Study - Effect of dronabinol on nutritional status in HIV infection.

1992 - Study - Dronabinol stimulates appetite and causes weight gain in HIV patients.

1992 - Study - Dronabinol effects on weight in patients with HIV infection.

1991 - Study - Recent clinical experience with dronabinol.

1990 - Study - Dronabinol enhancement of appetite in cancer patients.

1988 - Study - Effects of smoked marijuana on food intake and body weight.

1986 - Study - Behavioral analysis of marijuana effects on food intake in humans.

1982 - Study ~ Anorexia and hyperphagia produced by five pharmacologic classes of hallucinogens.

1976 - Study ~ Marihuana use. Biologic and behavioral aspects.

1972 - Study - Factors influencing the aggressiveness elicited by marihuana in food-deprived rats.

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Therapeutic Aspects of Cannabis and Cannabinoids


Background: Review commissioned in 1996 by the Department of Health (DOH).

Aims: Assess therapeutic profile of cannabis and cannabinoids.

Method: Medline search, references supplied by DOH and others, and personal communications.

Results and Conclusions: Cannabis and some cannabinoids are effective antiemetics and analgesics and reduce intraocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.

Declaration of interest: Funding from DOH. Between writing this paper and its acceptance for publication, P.R. was appointed Medical Director of GW Pharmaceuticals.


In 1996 I was commissioned by the Department of Health (DOH) to review the scientific literature regarding the potential therapeutic utility of cannabis and its derivatives. The review was based upon primary sources (identified from a Medline literature search, reference lists supplied by the DOH and the Institute for the Study of Drug Dependence, and personal communications with relevant academics and clinicians). This paper is a greatly shortened version of the review. The 4 years which have elapsed have seen little in the way of new clinical results but considerable advances in cannabinoid basic science (Institute of Medicine, 1999). Government licences have recently been granted for several controlled trials of both synthetic and plant-derived cannabinoids in multiple sclerosis and chronic pain. In January 2000, I was appointed Medical Director of GW Pharmaceuticals, a company established to derive medicinal extracts from standardised cannabis plants.

The first formal report of cannabis as a medicine appeared in China nearly 5000 years ago when it was recommended for malaria, constipation, rheumatic pains and childbirth and, mixed with wine, as a surgical analgesic (Mechoulam, 1986). There are subsequent records of its use throughout Asia, the Middle East, Southern Africa and South America. Accounts by Pliny, Dioscorides and Galen remained influential in European medicine for 16 centuries.

It was not until the 19th century that cannabis became a mainstream medicine in Britain. W. B. O'Shaughnessy, an Irish scientist and physician, observed its use in India as an analgesic, anticonvulsant, antispasmodic, anti-emetic and hypnotic. After toxicity experiments on goats and dogs, he gave it to patients and was impressed with its muscle-relaxant, anticonvulsant and analgesic properties, and recorded its usefulness as an anti-emetic.

After these observations were published in 1842, medicinal use of cannabis expanded rapidly. It soon became available 'over the counter' in pharmacies and by 1854 it had found its way into the United States Dispensatory. The American market became flooded with dozens of cannabis-containing home remedies.

Queen Victoria's personal physician wrote (Reynolds, 1890), on the basis of more than 30 years' experience, that "Indian hemp, when pure and administered carefully, is one of the most valuable medicines we possess". He found it incomparable for "senile insomnia", "night restlessness" and "temper disease" in both children and adults, but not helpful in melancholia, "very uncertain" in alcoholic delirium, and "worse than useless" in mania. It was very effective in neuralgia, period pains, migraine, "lightning pain of the ataxic patient" and gout, but useless in sciatica and "hysteric pains". He found it impressive in clonic spasms and certain epileptiform convulsions related to brain damage, but no good at all in petit mal or "chronic epilepsy", tetanus, chorea or paralysis agitans. It effectively relieved nocturnal cramps, asthma and dysmenorrhoea.

Reynolds was writing at a time when the zenith of cannabis as prescribed medicine and home remedy was already past. Although Sir William Osler was still recommending it for migraine sufferers in 1913, it was by then in steep decline because of variable potency of herbal preparations, poor storage stability, unpredictable response to oral administration, increasing enthusiasm for parenteral medicines and availability of potent synthetic alternatives, commercial pressures and American concern about recreational use. Cannabis was outlawed in 1928 by ratification of the 1925 Geneva Convention on the manufacture, sale and movement of dangerous drugs. Prescription remained possible until final prohibition under the 1971 Misuse of Drugs Act, against the advice of the Advisory Committee on Drug Dependence.

In the USA, medical use was effectively ruled out by the Marijuana Tax Act 1937. This ruling has been under almost constant legal challenge and many special dispensations were made between 1976 and 1992 for individuals to receive 'compassionate reefers'. Although this loophole has been closed, a 1996 California state law permits cultivation or consumption of cannabis for medical purposes, if a doctor provides a written endorsement. Similar arrangements apply in Italy and Canberra, Australia.

Cannabinol was isolated in 1895 and cannabidiol in 1934, but the most significant discovery was that of [DELTA]9-tetrahydrocannabinol (THC) in 1964. Chromatographic and spectroscopic methods subsequently uncovered many closely related compounds.

Capsules of synthetic THC (dronabinol) have been available for restricted medical use in the USA since 1985. Nabilone, a synthetic THC analogue, was marketed in 1983 and is the only cannabinoid licensed for prescription in the UK, restricted to treatment of nausea and vomiting caused by cytotoxic chemotherapy unresponsive to conventional anti-emetics. Use in other indications is only possible on a 'named patient' basis if the drug is supplied by a hospital pharmacy.

In 1988, a specific protein receptor (known as CB1) for THC was discovered in mouse nerve cells. This mediates most of the central nervous system (CNS) responses to cannabinoids, and is abundant in basal ganglia, hippocampus and cerebellum, globus pallidus, substantia nigra and cerebral cortex. An endogenous ligand was identified in 1992 and labelled anandamide (ananda: 'bliss' in Sanskrit). Anandamide has analgesic and tranquillising effects in animals, is involved in muscle coordination and affects the secretion and function of certain hormones. Other endogenous agonists almost certainly exist.

In 1993, a second receptor (CB2) was identified in rat spleen macrophages, and this occurs only outside the CNS. There is scope for chemical manipulation of cannabinoids to maximise selectivity for CB2 and so avoid psychoactive effects. It is thought this receptor has relevance for anti-inflammatory and immunosuppressive activity.

Pertwee (1995) has suggested that the anandamide system might be concerned with mood, memory and cognition, perception, movement, coordination, posture and skeletal muscle tone, sleep, thermoregulation, appetite and immune response.

Nausea and vomiting
Many cytotoxic drugs are powerful emetics, and this is the major limiting factor in patients' acceptance of cancer chemotherapy (see Table 1 and Appendix).


Table 1 Human randomised controlled trials (RCTs): anti-emetic effects

Many recreational smokers receiving cancer chemotherapy have told their doctors that cannabis relieved their nausea (Grinspoon & Bakalar, 1993). Sallan et al's (1975) randomised control trial (RCT) compared oral THC and placebo in 22 cancer patients who had proved resistant to conventional anti-emetics. Comparisons using patients' self-reports of nausea and vomiting demonstrated that THC was statistically superior to placebo. THC (10 mg/m2) produced euphoria in the majority of patients, and one-third experienced sedation.

Subsequent RCTs (listed in Table 1) confirmed that natural and synthetic THC is invariably superior to placebo. Comparisons with anti-emetics available in the 1970s and 1980s suggest that THC is either equivalent in effect or better. A combination of prochlorperazine and THC was superior to either drug alone, and nabilone combined with prochlorperazine was better than dexamethazone plus metoclopramide. Although THC and nabilone produced more unwanted effects than comparison drugs, patients generally preferred them.

Children seem to respond well to nabilone and are tolerant of side-effects, but larger studies are required. [DELTA]8-THC performed well in a pilot study (Abrahamov et al, 1995) involving eight children aged 3-13 years with various blood cancers receiving chemotherapy, 60% of whom had experienced distressing vomiting despite treatment with metoclopramide. [DELTA]8-THC was given orally 2 hours before cytotoxics and repeated 6-hourly. No vomiting was recorded during this treatment and over the following 2 days. Two children were "slightly irritable" and one also showed "slight euphoria".

In a review of 12 studies involving 600 patients (Penta et al, 1981), THC was "effective" in 8/9 and nabilone in 3/3. The most common side-effects were somnolence (33%), dry mouth (9%), ataxia (8%), dizziness (6%), dysphoria (6%), and orthostatic hypotension (4%). A further review (Levitt, 1986) incorporating 55 studies, of which 32 were RCTs, showed that low-dose preventive treatment gives better results than targeting established vomiting. Younger patients may respond better than older ones.

Meta-analysis (Plasse et al, 1991) suggested that an optimal balance of efficacy and unwanted effects was achieved with relatively modest doses (7 mg/m2 or less). Sedation and psychotropic symptoms are commonly reported, but are usually mild to moderate in intensity and resolve rapidly on discontinuation. No "persistent or fatal" adverse effects have been reported. Many American oncologists encourage nauseous patients to try cannabis and would prescribe it if it were legal (Doblin & Kleiman, 1991). Mode of action remains uncertain.

Multiple sclerosis and other neurological conditions
Drug therapy of muscle spasticity is generally only moderately effective and is limited by adverse effects (see Appendix). Spasticity is a central feature of multiple sclerosis (MS), cerebral palsy and spinal cord injury. Tremor, ataxia and incontinence also contribute to the high incidence of anxiety and depression in these conditions. Cannabis was often used to treat pain, muscle spasm, cramps and ataxia in the 19th century, and many modern sufferers have reported benefits (Grinspoon & Bakalar, 1993).

Most respondents to a questionnaire sent to British and American MS patients reported problems with symptom control (Consroe et al, 1997). Those who smoked cannabis claimed improvements in night-time spasticity and muscle pain (91-98%); night leg pain, depression, tremor, anxiety, spasms on walking, paraesthesiae (80-89%); leg weakness, trunk numbness, facial pain (71-74%); impaired balance (57%); constipation (33%); memory loss (31%).

In a small single-blind comparison with placebo (Clifford, 1983), THC improved tremor and ataxia in most patients. All experienced a 'high' at the top dose (15 mg), and two reported dysphoria. Dose-related improvements in dystonia were noted in five patients given cannabidiol 100-600 mg daily for 6 weeks. Hypotension, dry mouth, sedation and light-headedness occurred but were described as mild. Parkinsonian symptoms were aggravated in two subjects.

An RCT by Petro & Ellenberger (1981) compared the effects of placebo and THC in doses of 5 or 10 mg on muscle tone, reflexes and muscle power in nine MS patients. Both doses of THC reduced spasticity (P < 0.005). One patient receiving THC 10 mg and one patient receiving placebo felt 'high' but no other side-effects were recorded. In a small RCT (Ungerleider et al, 1987) with 5-day treatment periods, THC 7.5 mg significantly improved spasticity in comparison with placebo. Nabilone 1 mg on alternate days was compared with placebo in a double-blind randomised crossover trial with 4-week treatment periods in a single MS patient. Nocturia, muscle spasm and general well-being showed striking improvement during each active treatment period. Mild sedation was noted on active medication.

Cannabidiol had no beneficial effects in 15 patients with Huntington's disease (Consroe et al, 1991). Posture and balance were impaired by a single dose of smoked THC in 10 MS patients and 10 non-MS volunteers (Greenberg et al, 1994), but there was no active control to determine the effects of standard anti-spastic medication in this model.

Possible sites of action of cannabinoids in dystonia include basal ganglia, cerebellum, spinal motor neurons, somatic nerves and neuromuscular junction.

Loss of appetite and weight in cancer and AIDS
Several studies have investigated effect on appetite and weight (Table 2). The appetite-stimulating effect of cannabis was confirmed in fasting and non-fasting volunteers in an RCT of oral THC with alcohol, amphetamine and placebo (Hollister, 1971). A standardised THC smoking regime over 25 days in a residential laboratory was associated with significant increases in calorie intake and frequency of eating occasions in comparison with placebo.


Table 2 Human randomised controlled trials (RCTs): appetite and weight

Open studies in cancer patients also showed appetite improvements and slowing of weight loss. Regelson et al's (1976) RCT explored the effect on appetite (and mood) of oral THC in 54 cancer patients over a 2-week period. There were nine with-drawals due to side-effects (six in THC period - dizziness, disassociation, confused thinking, panic, "feelings of disturbance"; three in the placebo period - anxiety, fits, dizziness, lethargy, weakness). Patients receiving THC in the first period gained weight (P<0.05), and those receiving placebo first showed reduced weight loss on transfer to THC (P<0.05). Depression, tranquillity and "forthrightness" scores all improved on THC. In a quarter of the patients, somnolence, dizziness and disassociation were severe enough to negate these effects.

Many people with AIDS have claimed that smoking marijuana inhibits nausea, improves appetite, reduces anxiety, relieves aches and pains, improves sleep and inhibits oral candidiasis. A small pilot study supported the hypothesis that dronabinol might reduce weight loss or even promote weight gain (Plasse et al, 1991).

Beal et al (1995) conducted an RCT over 42 days of treatment with dronabinol 5 mg daily in 139 AIDS patients who had lost at least 2.3 kg. Six receiving dronabinol and three receiving placebo withdrew because of "perceived drug toxicity". Dronabinol boosted appetite in comparison to placebo (P<0.015) and nausea was reduced (P=0.05). Improvement in mood was a strong trend (P=0.06) and there was a tendency toward weight gain (P=0.1). Dronabinol produced more adverse effects than placebo (P<0.001), but 75% of these were mild or moderate. Most frequent were euphoria (9), dizziness (5), thinking abnormalities (5) and sedation (4).

Further investigation is amply justified. Careful monitoring of possible effects upon the immune system is needed, although a prospective multi-centre study (Kaslow et al, 1989), which followed nearly 5000 HIV-positive men for 18 months, showed no link between use of psychoactive substances and mean T-cell counts or progression to AIDS.

Cannabinoids are effective analgesics in animal models with non-opiate mechanisms predominating. There are many anecdotal reports (Grinspoon & Bakalar, 1993) of benefits in bone and joint pain, migraine, cancer pain, menstrual cramps and labour.

Five small RCTs (Table 3) show that THC is significantly superior to placebo and produces dose-related analgesia peaking at around 5 hours, comparable to but out-lasting that of codeine. Side-effects were also dose-related, and consisted of slurred speech, sedation and mental clouding, blurred vision, dizziness and ataxia. Levonantradol was also superior to placebo and notably long-acting, but almost half the patients reported sedation. Cannabinoids may have considerable potential in neuropathic pain (Institute of Medicine, 1999).


Table 3 Human randomised controlled trials (RCTs): pain

Raised intra-ocular pressure
Glaucoma due to obstructed outflow of aqueous humour or anatomical eye defects is the most common cause of blindness in the Western world. Some RCTs investigating this area are given in Table 4.


Table 4 Human randomised controlled trials (RCTs): raised intra-ocular pressure (IOP)

There have been many anecdotal reports that street marijuana can relieve glaucoma symptoms and individuals have successfully argued in the USA for legal access to the drug (Grinspoon & Bakalar, 1993). A pilot study of smoked marijuana and oral THC (15 mg) in 11 glaucoma patients found an average intra-ocular pressure (IOP) reduction of 30% in seven subjects and no response in four (Hepler et al, 1976).

Randomised controlled trials in volunteers confirmed that oral, injected or smoked cannabinoids produce dose-related reductions of IOP (Hepler et al, 1976; Perez-Reyes et al, 1976). Conjunctival engorgement and tear reduction were often noted. THC, [DELTA]8-THC and 11-hydroxy-THC are more effective than cannabinol, while cannabidiol was without effect. Tolerance may develop on multiple dosing.

An RCT in patients showed IOP reductions of similar magnitude following smoked THC along with "alterations in mental status" and tachycardia (Merritt et al, 1980). THC eyedrops produced dose-related IOP reduction with minimal side-effects though parallel reductions in the untreated eye (also seen in animal models) suggested a systemic rather than local mode of action.

Insomnia, anxiety and depression
Randomised controlled trials investigating insomnia, anxiety and depression are given in Table 5.


Table 5 Human randomised controled trials (RCTs): insomnia, anxiety, depression

Nabilone (1 mg three times daily) produced "dramatic improvements" on the Hamilton Anxiety Scale in 20 anxious patients in comparison to placebo (P<0.001), which were mirrored by other measures (Fabre & McLendon, 1981). Seven days into the study, nabilone patients' anxiety scores were halved, and this persisted unchanged throughout treatment. Side-effects included dry mouth, dry eyes and drowsiness. The authors concluded that nabilone is a "very effective anxiolytic deserving of further study". In a cross-over comparison of nabilone (1-2.5 mg twice daily) and placebo in 11 anxious patients (Ilaria et al, 1981), significant improvements in anxiety scores (P<0.05) were again noted. The only clinically significant adverse effect was postural hypotension with related dizziness, light-headedness or weakness. This was dose-related, experienced by most patients, and tended to tolerate out over time.

Preliminary data suggest that cannabidiol (160 mg) may be an effective hypnotic, and that THC (0.1 mg/kg) may have antidepressant properties in cancer patients and others (Grinspoon & Bakalar, 1993).

Epilepsy afflicts 1% of the world's population. Conventional anticonvulsants provide unsatisfactory control for up to 30% of patients, and all can produce disabling or even life-threatening adverse effects.

The effect of cannabinoids on seizure activity in laboratory animals is complicated. Cannabidiol is a powerful anti-convulsant free of tolerance, but its profile varies between species. THC can produce seizures in big doses or when genetically seizure-sensitive animals are used, yet it is also robustly anticonvulsant in certain seizure models. A lack of stereospecificity suggests that the mechanism may not be related to a single receptor interaction. Serotonin, [gamma]-aminobutyric acid, acetylcholine or prostaglandin systems may be involved.

There are many anecdotal reports of beneficial effects in humans with epilepsy (Grinspoon & Bakalar, 1993) but research data are virtually non-existent. Two single-case reports (Keeler & Reifler, 1967; Consroe et al, 1975) give confounding information. A young man suffered seizures on his regular medication and began smoking several cannabis cigarettes nightly alongside this. No further seizures occurred while this combination was maintained. In contrast, a man with grand mal epilepsy stopped taking anticonvulsants and suffered no fits for 6 months. He then smoked cannabis on seven occasions over a 3-week period and suffered three fits during this time, although not coincident with actual intoxication.

Only one RCT (Cunha et al, 1980) exists. Fifteen poorly controlled patients with secondary generalised epilepsy continued with their regular therapy but were also given either cannabidiol or placebo daily for up to 4.5 months while undergoing regular clinical and electroencephalogram evaluation. Half the patients on cannabidiol remained "almost free" of fits throughout the experiment, and all but one of the others showed "partial improvement". All but one of the placebo patients remained entirely unchanged. Somnolence occurred in four patients receiving cannabidiol.

Small-scale controlled studies in volunteers with asthma show that oral, smoked and aerosolised THC has comparable bronchodilatory activity to salbutamol, although onset is quicker with the latter. Dose-related tachycardia occurred in some individuals, and subjective intoxication with higher doses. A THC aerosol was free of systemic unwanted effects, but was irritant to the lungs (Tashkin et al, 1977). Nabilone does not produce bronchodilation. Since THC-induced bronchodilation is not mediated through the sympathetic nervous system, synergistic combinations with [beta]2-adrenoceptor stimulants might be possible.

Other possible therapeutic applications
Basic research indicates that THC and analogues inhibit opioid withdrawal (Chesher & Jackson, 1985). Anecdotal reports from patients also point to beneficial effects beyond those which could be accounted for by sedative or hypnotic activity. Cannabinoids inhibit primary tumour growth and increase survival in animal tumour models (Harris et al, 1976) by an unknown mechanism. They also show antipyretic and anti-inflammatory activity (Formukong et al, 1989). Mechoulam (1986) has drawn attention to the lack of modern research directed at possible antihelmintic, antimigraine and oxytocic applications.

Therapeutic profile on existing evidence
Tetrahydrocannabinol and nabilone are effective anti-emetics but there are no comparisons with 5-HT3 antagonists, so a role in modern anti-emetic regimes remains to be determined. Currently, only nabilone is licensed in the UK and available for prescription and research. THC (as dronabinol) has recently been rescheduled to permit prescription but remains unlicensed and must be specially imported on a named-patient basis. Delta-8-THC looks worthy of further investigation, particularly in children, and is much simpler to synthesise than THC.

Many individuals with MS have claimed a benefit from cannabis and small controlled trials support this, although effect upon posture and balance requires clarification. THC is an effective analgesic at the expense of sedation with larger doses and may have special merit in neuropathic pain. No conclusions are possible as yet about anticonvulsant potential. Some cannabinoids reduce IOP, though side-effects of products currently available limit application and effects of tolerance are uncertain. The mechanism for bronchodilation probably differs from that of [beta]2-stimulants, so synergistic combinations may be possible.

Cannabis and THC are effective appetitc stimulants. Alongside anti-emetic, analgesic, anxiolytic, hypnotic and antipyretic properties this suggests a unique role in alleviating symptoms in selected patients with cancer or AIDS. This is a compelling area for future research, although possible effects upon immune function require careful monitoring.

Optimal doses and routes of delivery have not been established. Absorption by the oral route is unreliable. Smoking the drug is generally not a viable option since advantages such as rapid onset, accurate titration of effects and reliability in patients who are vomiting have to be set against the likelihood of lung irritation or damage, and it would in any case be unacceptable to most patients. However, pending availability of more satisfactory preparations, I believe that the existing profile of efficacy and toxicity justifies the provision of a legal supply of standardised herbal material ('compassionate reefers') to patients with terminal conditions who currently obtain relief with street cannabis. Sublingual sprays or tablets, nebulisers and aerosols look promising for the future, and THC is effective by the rectal route. Many potentially active cannabinoids have yet to be investigated and the recent identification of a peripheral receptor may lead to new drugs devoid of central nervous system effects.

Cannabis arouses passion in those who support or condemn it, and few people approach the clinical literature with dispassionate objectivity. Poorly controlled research produces ambiguous results which are then interpreted according to the prejudices of the reader. Anecdotes seem to be more readily accepted when they point to adverse rather than positive effects (Hall et al, 1994). Yet the known adverse effects of oral cannabinoids are rarely intolerable or life-threatening, in contrast to those associated with some standard therapies. A British Medical Association survey indicated that many UK doctors believe that cannabis should once again be available on prescription (Meek, 1994).

The way forward
A Select Committee of the House of Lords recently examined the scientific information concerning medical cannabis and took verbal and written evidence from a wide range of witnesses. Their conclusion (House of Lords, 1998) published in November 1998, was that, although cannabis should remain a controlled drug, the law should be changed to allow doctors to prescribe "an appropriate preparation of cannabis if they saw fit". The government rejected this recommendation on the day of publication.

Under the auspices of the Royal Pharmaceutical Society, large-scale multi-centre trials are under way to explore further the efficacy of cannabinoids in relieving spasticity and postoperative pain. A pharmaceutical company has obtained a licence to cultivate medicinal cannabis on a large scale in the UK. By selecting a specific genotype then carefully controlling all other relevant variables such as soil conditions, temperature and humidity, it is possible to obtain levels of purity in plant extracts equal or superior to those of 'pure' synthetic cannabinoids. Most of the 60 or so naturally occurring cannabinoids are present in tiny amounts, and synthetic cannabinoids such as nabilone themselves contain up to 5% impurities, some of which are of unknown identity. Whether obtained by synthetic means or by plant extraction, it is essential that cannabinoids for prescription and research in the future should demonstrate excellent purity, stability and bioavailability.

The medicinal properties of cannabis are still mainly delineated by the anecdotal reports of those who believe their symptoms are relieved by its use, and these accounts are often dismissed as wishful thinking or even mischievous. Since the conventional treatments for many of these disorders are both toxic and relatively ineffectual, a more constructive response would be to expose such claims to careful scientific examination and, in the meantime, search for a way to avoid criminalising those who seek only to assuage their own suffering.

* Cannabis and its derivatives show promise of beneficial effects in a number of medical conditions for which standard treatment is less than satisfactory, and further controlled research is fully justified.
* Cannabis is very safe in overdose, but often produces unwanted effects which are better tolerated by patients with some conditions (e.g. multiple sclerosis, chronic pain, AIDS, cancer) than others (e.g. glaucoma).
* Optimal for mutations, doses and routes of delivery have not yet been established.

* Because of imposed time constraints, the review is not fully comprehensive, although all accessed sources were incorporated.
* Much of the evidence is anecdotal, and many of the research studies cited have serious methodological shortcomings.
* Few researchers (or reviewers) approach the subject of cannabinoid therapeutics in a spirit of dispassionate objectivity.

This review was originally commissioned and funded by the Department of Health. The author thanks Dr Anthony Thorley for his support and encouragement. The views expressed in the paper are those of the author and not necessarily of the Department of Health.

Existing anti-emetics
Phenothiazzines and butyrophenones can cause sedation, movement disorders which may be irreversible, neuroleptic malignant syndrome, dry mouth, blurred vision, urinary retention, hypotension, allergic reactions, jaundice, hypothermia, hormonal disturbances, irreversible eye damage and, rarely, life-threatening anaemias. Domperidone has a more benign profile but is not recommended for long-term use. Metoclopramide produces movement disorders (1% of patients), dizziness and drowsiness. Selective 5-HT3 antagonists (ondansetron, granisetron) are newer and more expensive. Side-effects include constipation, headache, flushing, liver enzyme changes, allergic reactions, visual disturbances, chest pain and dysrhythmias.

Existing neurological treatments
Baclofen alleviates spasticity, but may accentuate muscle weakness. It produces dose-related nausea and vomiting, drowsiness, vertigo, confusion, fatigue and hypotonia. Less commonly, fits, psychiatric disorder and hypotension occur. Sudden withdrawal can cause hallucinations. Diazepam is useful but can worsen weakness or incoordination and cause drowsiness; ataxia, depression, disinhibition and dependence. Dantrolene may cause weakness, hypotonia, drowsiness, dizziness, vertigo and anxiety. Rarely, it damages the liver, and is not recommended in those with co-existing heart or lung disease.

Existing glaucoma treatments
Eye-drops. Miotics can produce blurring of vision, headache, and parasympathetic effects including sweating, bradycardia, colic and bronchospasm. Adrenaline often causes local discomfort. Dipivefrine and guanethicline may cause conjunctival fibrosis on chronic use. Beta-blockers may cause bradycardia, heart block or bronchoconstriction.

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Ungerleider, J. T., Andrysiak, T., Fairbanks, L., et al (1987) Delta-9-THC in the treatment of spasticity associated with multiple sclerosis. Advances in Alcoholism and Substance Abuse, 7, 39-50. [Context Link]



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THC improves appetite and reverses weight loss in AIDS patients

TitleTHC improves appetite and reverses weight loss in AIDS patients
Author(s)Dejesus E, Rodwick BM, Bowers D, Cohen CJ, Pearce D
Journal, Volume, IssueJ Int Assoc Physicians AIDS Care 2007;6(2):95-100.
Major outcome(s)THC improved appetite and weight and reduced nausea
IndicationNausea/vomiting;Appetite loss/weight loss;HIV/AIDSAbstract

Objective: To determine whether dronabinol affects appetite and weight status in patients living with HIV/AIDS. METHODS: A retrospective chart review was conducted to analyze weight and appetite changes and nausea status in patients with HIV/AIDS who received dronabinol for 3 to 12 months from January 11, 1993, to March 17, 2003. RESULTS: Of the 117 patients who lost weight before baseline, 63% maintained or gained weight. In patients receiving dronabinol for 1 year, the mean weight gain (+/- SD) was 3.7 +/- 10.6 lb. The percentage of patients experiencing loss of appetite decreased significantly from 71% at baseline to 26% at 1 month (P < .001) and continued to decline throughout the trial. The percentage of patients experiencing nausea at baseline (38%) decreased consistently from week 2 on; this change from baseline was significant at month 6 (P = .031). CONCLUSION: When taken for 3 months to 1 year, dronabinol significantly improves appetite and reverses weight loss in patients living with HIV/AIDS.

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Duration (days)90-365
Participants117 patients with HIV/AIDS
DesignOpen study
Type of publicationMedical journal
Address of author(s)Orlando Immunology Center, Orlando, Florida, edejesus@oicorlando.com.
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Efficacy of dronabinol alone and in combination

TitleEfficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting.
Author(s)Meiri E, Jhangiani H, Vredenburgh JJ, Barbato LM, Carter FJ, Yang HM, Baranowski V.
Journal, Volume, IssueCurr Med Res Opin 2007;23(3):533-43.
Major outcome(s)Dronabinol was as effective as ondansetron in reducing nausea and vomiting. Combination therapy was not more effective.
IndicationNausea/vomiting;Cancer;Cancer chemotherapyAbstract

OBJECTIVE: To compare the efficacy and tolerability of dronabinol, ondansetron, or the combination for delayed chemotherapy-induced nausea and vomiting (CINV) in a 5-day, double-blind, placebo-controlled study. RESEARCH DESIGN AND METHODS: Patients receiving moderately to highly emetogenic chemotherapy received dexamethasone (20 mg PO), ondansetron (16 mg IV) and either placebo or dronabinol (2.5 mg) prechemotherapy on day 1. Patients randomized to active treatment (dronabinol and/or ondansetron) also received dronabinol (2.5 mg) after chemotherapy on day 1. On day 2, fixed doses of placebo, dronabinol (10 mg), ondansetron (16 mg), or combination therapy were administered. On days 3-5, patients received placebo, flexible doses of dronabinol (10-20 mg), ondansetron (8-16 mg), or dronabinol and ondansetron (10-20 mg dronabinol, 8-16 mg ondansetron). MAIN OUTCOME MEASURES: Total response (TR = nausea intensity <5 mm on visual analog scale, no vomiting/retching, no rescue antiemetic), nausea (occurrence and intensity) and vomiting/retching episodes. RESULTS: Sixty-four patients were randomized; 61 analyzed for efficacy. TR was similar with dronabinol (54%), ondansetron (58%), and combination therapy (47%) versus placebo (20%). Nausea absence was significantly greater in active treatment groups (dronabinol, 71%; ondansetron, 64%; combination therapy, 53%) versus placebo (15%; p < 0.05 vs. placebo for all). Nausea intensity and vomiting/retching were lowest in patients treated with dronabinol. Active treatments were well tolerated. The low number of patients due to slow enrollment limits the interpretation of these data. CONCLUSIONS: Dronabinol or ondansetron was similarly effective for the treatment of CINV. Combination therapy with dronabinol and ondansetron was not more effective than either agent alone. Active treatments were well tolerated.

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Dose(s)10-20 mg
Duration (days)5
Participants64 patients undergoing chemotherapy
DesignControlled study
Type of publicationMedical journal
Address of author(s)Bethesda Memorial Hospital, Comprehensive Cancer Care Center, Boynton Beach, FL 33435-7995, USA. mdeyal@hotmail.com
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Dronabinol and marijuana in HIV-positive marijuana smokers: caloric intake, mood, and sleep

Margaret Haney et al, "Dronabinol and Marijuana in HIV-Positive Marijuana Smokers,
Caloric Intake, Mood, and Sleep," Journal of Acquired Immune Deficiency Syndromes 45, issue 5 (August 15, 2007): 545-554.

This clinical trial found that both smoked marijuana and the THC pill (Marinol, known generically as dronabinol) are effective at increasing caloric intake and weight among HIV-positive patients, with no effect on cognitive performance. Strikingly, however, it took eight times the standard dose of Marinol to approximate the effect of weak (3.9% THC) marijuana, and even at that dose, natural marijuana outperformed Marinol in some measurements.

The full study is available for free download here: http://journals.lww.com/jaids/Fulltext/2007/08150/Dronabinol_and_Marijuana_in_HIV_Positive_Marijuana.9.aspx?desktopMode=true


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Dronabinol an effective appetite stimulant

TitleAnorexia of aging in long term care: is dronabinol an effective appetite stimulant? - a pilot study.
Author(s)Wilson MM, Philpot C, Morley JE
Journal, Volume, IssueJ Nutr Health Aging. 2007 Mar-Apr;11(2):195-8.
Major outcome(s)A trend towards weight gain
IndicationAppetite loss/weight lossAbstract

Introduction: Anorexia and subsequent weight loss increase the risk of death in long term care (LTC) residents. In patients who fail to respond to nutritional intervention, orexigenic drugs are sometimes prescribed. There is limited data regarding the safety and efficacy of these drugs in older adults. Objective: To examine the effect of a 12-week course of dronabinol on LTC residents with anorexia and significant weight loss. Design, setting, participants: Retrospective observational study on residents in five LTC facilities in a major metropolitan area. Results: Twenty-eight subjects (22F, 6M) were involved in the study. Mean age 79.5 +/- 19.8 years (range 46-98y). Mean body weight, serum albumin and serum prealbumin at baseline were 105.7 +/- 24.7 lbs, 3.39 +/- 0.47 g/dl and 22.15 +/- 7.92 mg/dl respectively. 15 subjects (53.5%) gained weight on dronabinol, of which 10 (67%) gained more than 5lbs and 6(40%) gained more than 10lbs. Five (33%) subjects gained less than 5lbs. Residents who lost weight on dronabinol were younger than those who gained weight (70.9 +/- 5.62 y and 90.8 +/- 7.84 y respectively; p = 0.007) Overall, the mean weight gain on dronabinol was 3 +/- 8.01 lbs (p=0.2). Eleven subjects lost weight (mean loss 3 +/- 2.6 lbs). Of the subjects who lost weight 7 (64%) died compared with 4 (26%) in the subgroup who gained weight. Conclusions: Dronabinol therapy was well tolerated. Overall, there was a trend toward weight gain in LTC residents treated with 12 weeks of dronabinol. Failure to respond to dronabinol may indicate increased risk of death.


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Duration (days)84
Participants28 old patients suffering from weight loss
DesignOpen study
Type of publicationMedical journal
Address of author(s)M.M.G. Wilson, MRCP, Division of Geriatric Medicine, Saint Louis University, 1402, S. Grand Blvd, Rm M238, St Louis, MO 63104, Tel: (314) 977-8404, Fax: (314) 977-8409, Email: wilsonmg@slu.edu.
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The synthetic cannabinoid nabilone improves pain and symptom management in cancer patients

TitleThe synthetic cannabinoid nabilone improves pain and symptom management in cancer patients
Author(s)Maida V.
Journal, Volume, IssueAbstract presented at the San Antonio Breast Cancer Symposium on 15 December 2006
Major outcome(s)Nabilone treatment improved pain, nausea, appetite and several other symptoms
IndicationNausea/vomiting;Appetite loss/weight loss;Cancer;Pain;Depression;AnxietyAbstract

Background: Cancer patients experience numerous disease-related symptoms and side effects of treatment, such as pain, nausea, anorexia, anxiety, among others. Despite the use of the current drugs of first choice, many patients continue to suffer intractably from a number of symptoms. This impacts negatively on their quality of life, functional status, and their desire to continue with disease altering therapies. The synthetic cannabinoid, nabilone (Cesamet), is officially indicated for the treatment of refractory chemotherapy-induced nausea and vomiting. Pre-clinical studies and preliminary findings from clinical trials suggest cannabinoids may be useful for the management of multiple symptoms and side effects in cancer patients. Nabilone offers the opportunity to optimize pain and symptom management while reducing overall polypharmacy.
Material and Methods: Data were retrospectively collected from the charts of patients referred to a specialist consultative palliative medicine program in a large urban centre between May 1, 2005 and June 30, 2006. The decision to prescribe nabilone was based on the presence of severe pain and symptom distress. The sample was selected on the basis that they had completed an Edmonton Symptom Assessment System (ESAS) questionnaire on the initial consultation, and then, at least one thereafter. Data from a total of 139 patients were reviewed, of which nabilone was prescribed to 82. All patients were followed by a specialist team consisting of a palliative medicine physician and nurse practictioner. ESAS questionnaires were completed on their initial consultation and serially thereafter. Although 17 patients discontinued nabilone owing to side effects or based on the recommendation of other treating physicians, their follow-up continued. In addition, serial performance status, measured by the Palliative Performance Scale, version 2 (PPSv2), and a recording of all other medications employed was documented. Data analysis was carried out by an academic biostatistical consultant using MS Windows based S-Plus 6.2 software. The change in ESAS score on all 10 items was compared between the cannabinoid and non-cannabinoid subjects.
Results. The mean baseline PPSv2 was 56.7 ( 15.4) in the cannabinoid subjects and 53.9 ( 14.8) in the non-cannabinoid subjects; duration of follow-up (mean) was similar between the two groups (nabilone, 52.8 [ 80.3] days; non-nabilone, 51.6 [ 72.5] days). Compared with non-cannabinoid subjects, the nabilone subjects experienced significant (P<.0001) reductions in pain, markedly so in subjects with a PPS.v2 score of 60 or higher. For drowsiness, tiredness, appetite, and well-being, ESAS scores remained stable in the nabilone group but deteriorated in the non-nabilone group. While subjects in the nabilone group had significantly (P<.0001) greater nausea at baseline, they experienced a significant reduction (P<.0001), in contrast to non-cannabinoid subjects. Depression and anxiety were significantly (P<.0001) more prevalent in the nabilone group; however, reductions in both symptoms were significant (P<.0001) with use of the cannabinoid. Conversely, anxiety and depression increased in the non-cannabinoid group. Item No. 10 on the ESAS, Other, allows patients to rate a particularly bothersome symptom. Two symptoms emerged as important in nabilone subjects: insomnia and fever/night sweats. For both these symptoms, nabilone appeared to be efficacious. Distress, which is derived from scores on the first nine items of ESAS, improved significantly (P<.0001) in subjects receiving nabilone in contrast to non-cannabinoid subjects.
Discussion: The study findings are limited by potential biases. Imbalances between the two groups in baseline scores were not adjusted, and the time to the last measurement, from which change in scores was calculated, was variable. The standard of care in the two groups also was not documented. Nonetheless, nabilone, when added to standard of care and taken longer-term, appears to offer significant alleviation of several symptoms in cancer patients, including pain, nausea, depression and anxiety, insomnia, fever/night sweats, and overall distress.


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Duration (days)53
Participants139 cancer patients
DesignOpen study
Type of publicationMeeting abstract
Address of author(s)University of Toronto; William Osler Health Center, Toronto, Canada
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Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases

Title[Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases.] [Article in German]
Author(s)Zutt M, Hanssle H, Emmert S, Neumann C, Kretschmer L.
Journal, Volume, IssueHautarzt 2006;57(5):423-7.
Major outcome(s) A significant increase in appetite and decrease in nausea in most patients.
IndicationNausea/vomiting;Appetite loss/weight loss;Cancer;Cancer chemotherapyAbstract

BACKGROUND: Loss of appetite and nausea can reduce the quality of life of patients with malignant melanoma and liver metastases. Often established antiemetic drugs fail to bring relief. Tetrahydrocannabinol (THC, Marinol (TM)), which is the active agent of Indian hemp, has been used successfully in this situation for other malignant tumors.PATIENTS AND METHODS: We treated 7 patients with hematogenous metastatic melanoma and liver metastases suffering from extensive loss of appetite and nausea supportively with dronabinol (Marinol((R))). All of these patients had previously received standard antiemetic therapy without adequate relief. Dronabinol is a synthetic Delta-tetrahydrocannabinol. The drug was administered in capsule form. We evaluated the palliative effects of dronabinol with a special patient evaluation form, which was filled out at the beginning of the therapy and again after 4 weeks.RESULTS: The majority of patients described a significant increase in appetite and decrease in nausea. These effects remained for some weeks, but then decreased as metastases progressed and the general condition worsened. All of the patients experienced slight to moderate dizziness, but it was not sufficiently troubling to cause interruption or termination of therapy.CONCLUSION: Loss of appetite and nausea due to liver metastases of malignant melanoma can be treated in individual cases supportively with Dronabinol.


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Duration (days) 
Participants7 patients with hematogenous metastatic melanoma
DesignOpen study
Type of publicationMedical journal
Address of author(s)Hautklinik und Poliklinik der Georg-August-Universitat Gottingen, Germany
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Safety and efficacy of dronabinol in the treatment of agitation in patients with Alzheimer's disease

TitleSafety and efficacy of dronabinol in the treatment of agitation in patients with Alzheimer’s disease with anorexia: A retrospective chart review
Author(s)Patel S, Shua-Haim JR, Pass M
Journal, Volume, IssueAbstract, International Psychogeriatric Association, Eleventh International Congress, 2003
Major outcome(s)Weight gain in all, reduction of agitation in 65%.
IndicationAppetite loss/weight loss;Alzheimer's diseaseAbstract

Objective: to investigate the safety and efficacy of dronabinol in Alzheimer’s disease (AD) patients with agitation.
Design: retrospective review.
Materials and Methods: AD patients with anorexia, where according to family members or caregivers (staff nurses) agitation was not satisfactorily controlled, were prescribed dronabinol. All met the DSM-IV & NINCDS-ADRDA criteria for possible AD. There were no exclusion criteria. Study subjects resided in a dementia unit in assistant living facility and in a nursing home. Dronabinol, 5 mg/day in 2 divided doses was given initially & titrated up to a maximum of 10 mg/day. Cognition and function evaluated at the start and end of the study period. MMSE and ADL scales used for assessment. Concomitant medications were recorded. After 1 month of treatment, caregivers were asked to complete a questionnaire regarding their impression on treatment efficacy.
Results: 48 patients were treated with dronabinol. Average age was 77. Average MMSE was 16. All patients were treated with atypical neuroleptics. All were treated with multiple (greater than 3) medications to control behavior. All patients had diagnoses of anorexia prior to initiation of dronabinol therapy. Weight gain was reported in all patients. Agitation significantly improved in 31 (65%). In 14 (37%) there was improvement in MMSE score (average increase by 1.6 points (range +1 to +3). Functional improvement was reported in 33 (69%). 17 (35%) patients had no significant beneficial effect with regard to agitation, and their medication was discontinued within 2 weeks of initiation of treatment. No patient experienced any significant adverse event (falls, syncope, seizures or exacerbation of agitation/depression).
Conclusion: Dronabinol treatment for agitation in AD patients with anorexia was effective in 31 out of 48 of patients who were refractory to other medications. No adverse events were reported.

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Duration (days)30
Participants48 Alzheimer patients
DesignOpen study
Type of publicationMeeting abstract
Address of author(s)Meridian Institute for Aging, Manchester Township, NJ, USA
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The perceived effects of smoked cannabis on patients with multiple sclerosis

TitleThe perceived effects of smoked cannabis on patients with multiple sclerosis.
Author(s)Consroe P, Musty R, Rein J, Tillery W, Pertwee R
Journal, Volume, IssueEuropean Neurology 1997;38(1):44-48
Major outcome(s)In more than 80% improvement of spasticity, pain, tremor, depression, anxiety, and paresthesia
IndicationSpasticity;Multiple sclerosis;Pain;Tremor;DepressionAbstract

Fifty-three UK and 59 USA people with multiple sclerosis (MS) answered anonymously the first questionnaire on cannabis use and MS. From 97 to 30% of the subjects reported cannabis improved (in descending rank order): spasticity, chronic pain of extremities, acute paroxysmal phenomenon, tremor, emotional dysfunction, anorexia/weight loss, fatigue states, double vision, sexual dysfunction, bowel and bladder dysfunctions, vision dimness, dysfunctions of walking and balance, and memory loss. The MS subjects surveyed have specific therapeutic reasons for smoking cannabis. The survey findings will aid in the design of a clinical trial of cannabis or cannabinoid administration to MS patients or to other patients with similar signs or symptoms.

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Duration (days)months to years
Participants112 patients with multiple sclerosis
Type of publication 
Address of author(s)Department of Pharmacology/Toxicology, University of Arizona Health Sciences Center, Tucson, USA
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Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease

TitleEffects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease.
Author(s)Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ
Journal, Volume, IssueInternational Journal of Geriatric Psychiatry 1997;12(9):913-919
Major outcome(s)higher weight gain with THC; reduction of disturbed behaviour with THC
IndicationAppetite loss/weight loss;Alzheimer's diseaseAbstract

A placebo-controlled crossover design, with each treatment period lasting 6 weeks, was used to investigate effects of dronabinol in 15 patients with a diagnosis of probable Alzheimer's disease who were refusing food. Eleven patients completed both study periods; one patient who died of a heart attack 2 weeks before the end of the study was also included in the analysis. The study was terminated in 3 patients: one developed a grand mal seizure and 2 developed serious intercurrent infections. Body weight of study subjects increased more during the dronabinol treatment than during the placebo periods. Dronabinol treatment decreased severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first. Adverse reactions observed more commonly during the dronabinol treatment than during placebo periods included euphoria, somnolence and tiredness, but did not require discontinuation of therapy. These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer's disease.

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Duration (days)42
Participants15 patients with Alzheimer's disease
DesignControlled study
Type of publication 
Address of author(s)E. N. Rogers Memorial Veterans Hospital, Geriatric Research Education Clinical Center, Bedford, MA, USA
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Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS

TitleDronabinol as a treatment for anorexia associated with weight loss in patients with AIDS.
Author(s)Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, Lefkowitz L, Plasse TF, Shepard KV
Journal, Volume, IssueJournal of Pain and Symptom Management 1995;10(2):89-97
Major outcome(s)increased appetite; improvement in mood; stabel weight
IndicationAppetite loss/weight loss;HIV/AIDS;DepressionAbstract

The effects of dronabinol on appetite and weight were evaluated in 139 patients with AIDS-related anorexia and > or = 2.3 kg weight loss in a multi-institutional study. Patients were randomized to receive 2.5 mg dronabinol twice daily or placebo. Patients rated appetite, mood, and nausea by using a 100-mm visual analogue scale 3 days weekly. Efficacy was evaluable in 88 patients. Dronabinol was associated with increased appetite above baseline (38% vs 8% for placebo, P = 0.015), improvement in mood (10% vs -2%, P = 0.06), and decreased nausea (20% vs 7%; P = 0.05). Weight was stable in dronabinol patients, while placebo recipients had a mean loss of 0.4 kg (P = 0.14). Of the dronabinol patients, 22% gained > or = 2 kg, compared with 10.5% of placebo recipients (P = 0.11). Side effects were mostly mild to moderate in severity (euphoria, dizziness, thinking abnormalities); there was no difference in discontinued therapy between dronabinol (8.3%) and placebo (4.5%) recipients. Dronabinol was found to be safe and effective for anorexia associated with weight loss in patients with AIDS.

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Dose(s)2.5 mg twice daily
Duration (days)42
Participants139 patients with AIDS
DesignControlled study
Type of publication 
Address of author(s)St. John's Hospital, Tulsa, Oklahoma, USA
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Delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia

TitleA phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia.
Author(s)Nelson K, Walsh D, Deeter P, Sheehan F
Journal, Volume, IssueJournal of Palliative Care 1994;10(1):14-18
Major outcome(s)increase of appetite in 13 patients
IndicationAppetite loss/weight loss;CancerAbstract

Purpose: To evaluate the appetite-stimulating properties of delta-9- tetrahydrocannabinol (THC) in patients with anorexia due to advanced cancer. Patients and methods: Nineteen patients with various malignancies were entered. All had cancer-associated anorexia and a life expectancy greater than four weeks. Patients were started on THC 2.5 mg p.o. t.i.d. one hour after meals for four weeks. Evaluations for side effects, efficacy, acceptability and satisfaction were conducted at two and four weeks. Results: 18 patients were evaluable. Ten patients completed the entire 28-day study. Four patients experienced grade I toxicity and three withdrew at their request. Thirteen patients reported an improved appetite. Conclusion: THC is an effective appetite stimulant in patients with advanced cancer. It is well tolerated at low doses. Further studies are needed to determine the most appropriate dose and the specific population most likely to respond.

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Dose(s)2.5 mg three times daily
Duration (days)28
Participants18 patients with cancer evaluable
DesignOpen study
Type of publication 
Address of author(s)Palliative Care Program, Cleveland Clinic Foundation Ohio, USA
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Effect of dronabinol on nutritional status in HIV infection

TitleEffect of dronabinol on nutritional status in HIV infection.
Author(s)Struwe M, Kaempfer SH, Geiger CJ, Pavia AT, Plasse TF, Shepard KV, Ries K, Evans TG.
Journal, Volume, IssueAnn Pharmacother. 1993 Jul-Aug;27(7-8):827-31.
Major outcome(s)Trends toward weight gain, improved appetite, decreased symptom stress
IndicationAppetite loss/weight loss;HIV/AIDSAbstract

OBJECTIVE: To examine the effect of dronabinol (delta-9-tetrahydrocannabinol) on appetite and nutritional status in patients with symptomatic HIV infection and weight loss. DESIGN: Double-blind, randomized, placebo-controlled, crossover trial with two five-week treatment periods separated by a two-week washout period. Patients received dronabinol 5 mg twice daily before meals or placebo. SETTING: A university-based HIV/AIDS clinic and a large infectious disease private practice largely devoted to care of patients with HIV. PARTICIPANTS: Twelve HIV-infected patients who had had at least a 2.25-kg weight loss participated in the study. Five patients completed the protocol, and seven withdrew (two because of drug intolerance, two because of disease progression, two because of noncompliance, and one because of experimental antiretroviral therapy). MAIN OUTCOME MEASURES: Main outcome measures included caloric intake, weight, percent body fat, serum prealbumin, and symptom distress. RESULTS: During dronabinol treatment, subjects experienced increased percent body fat (one percent, p = 0.04); decreased symptom distress (p = 0.04); and trends toward weight gain (0.5 kg, p = 0.13), increased prealbumin (29.0 mg/L, p = 0.11), and improved appetite score (p = 0.14). CONCLUSIONS: In a selected group of HIV-infected patients with weight loss, short-term treatment with dronabinol may result in improvement in nutritional status and symptom distress.

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Dose(s)5 mg twice daily
Duration (days)84
Participants12 HIV patients.
DesignControlled study
Type of publicationMedical journal
Address of author(s)Division of Foods and Nutrition, University of Utah, Salt Lake City.
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Dronabinol stimulates appetite and causes weight gain in HIV patients

TitleDronabinol stimulates appetite and causes weight gain in HIV patients.
Author(s)Plasse T, Conant M, Gorter R, Shepard KV
Journal, Volume, IssueInternational Conference on AIDS 1992;8(3):122 (abstract no. PuB 7442)
Major outcome(s)increase in appetite, trend toward weight gain
IndicationHIV/AIDS; Appetite loss/weight loss; DepressionAbstract

OBJECTIVE: To test the effect of dronabinol (delta-9- tetrahydrocannabinol) on appetite and weight in symptomatic HIV patients (pts). METHODS: Forty pts with symptomatic HIV infection who were actively losing weight were entered into this dose ranging study of dronabinol (Marinol, Roxane Laboratories, Columbus OH). After a one week baseline period, pts were treated for 4 weeks; to be evaluable for efficacy, patients had to receive at least 3 weeks' medication. Pts were weighed and completed a questionnaire on physical and psychological symptoms weekly; they completed 100mm visual analog scales for hunger before each meal. Of 40 pts entered, 10 withdrew due to suspected adverse effects of study medication and 7 due to other causes. RESULTS: TABULAR DATA, SEE ABSTRACT VOLUME. CONCLUSIONS: In this open pilot study, dronabinol 2.5 mg bid was well tolerated and caused a significant increase in appetite, improvement of symptoms and a strong trend toward weight gain.


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Dose(s)2.5 mg twice daily
Duration (days)28
Participants40 patients with AIDS
DesignControlled study
Type of publication 
Address of author(s)UNIMED Inc., Somerville, NJ., USA
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Dronabinol effects on weight in patients with HIV infection

TitleDronabinol effects on weight in patients with HIV infection.
Author(s)Gorter R, Seefried M, Volberding P
Journal, Volume, IssueAIDS 1992;6(1):127
Major outcome(s)weight gain
IndicationAppetite loss/weight loss;HIV/AIDSAbstract

[Excerpt :]
Dronabinol effects on weight in patients with HIV infection
Weight loss is a major characteristic of symptomatic HIV infection and appears to be a prognostic factor in death from AIDS. Anecdotally, smoking marijuana has been noted to cause appetite stimulation in uninfected subjects. In addition, some AIDS patients who smoke marijuana have noted improved appetite and weight stabilization or gain. In controlled studies in normal volunteers and cancer patients, dronabinol [..] has been noted to cause weight gain and increase appetite. We therefore treated 12 symptomatic HIV-infected patients with dronabinol in an attempt to improve appetite and control weight loss. [..]

Patients were treated with dronabinol (Marinol, Roxane Laboratories, Columbus, Ohio, USA) at a starting dose of 2.5 mg orally three times daily. Doses, which were adjusted to minimize side-effects while stimulating appetite, ranged from 2.5 mg twice daily to 5 mg four times daily. Most patients were continuing treatment at the time of this analysis; the median duration of treatment was >= 12 weeks (range, > 4 to >20 weeks). [..]

All patients tolerated therapy well. They were able to adjust the medication dose to avoid unwanted THC side-effects, such as sedation and persistent euphoria. No patient discontinued therapy because of side-effects. Seven of the patients gained weight while on therapy and two others lost less than they had prior to therapy. Both patients who had previously received megestrol gained weight on dronabinol. The patient concurrently on megestrol lost weight, but slightly less rapidly than before starting dronabinol. While no formal measurements of body composition were performed, there was no clinical evidence that weight gain was due to fluid retention. [..]

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Dose(s)2.5-5 mg twice to four times daily
Duration (days)28-140
Participants12 patients with AIDS
DesignOpen study
Type of publicationMedical journal
Address of author(s) 
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Recent clinical experience with dronabinol

TitleRecent clinical experience with dronabinol.
Author(s)Plasse TF, Gorter RW, Krasnow SH, Lane M, Shepard KV, Wadleigh RG
Journal, Volume, IssuePharmacol Biochem Behav. 1991 Nov;40(3):695-700.
Major outcome(s)Significant weight gain
IndicationAppetite loss/weight loss;HIV/AIDSAbstract

Dronabinol, delta-9-tetrahydrocannabinol in sesame oil, has been used for several years as an antiemetic for patients receiving cancer chemotherapy. In combination studies with prochlorperazine, enhancement of efficacy, as measured by duration of episodes of nausea and vomiting and by severity of nausea, has been found. The incidence of psychotropic effects from dronabinol appears to be decreased by concomitant administration of prochlorperazine. In open pilot studies, dronabinol caused weight gain in seven of ten patients with symptomatic HIV infection. In both HIV and cancer patients, dronabinol improved appetite at a dose which was well tolerated for chronic administration.

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Dose(s)THC 2x2.5 mg for 5 months
Duration (days) 
Participants10 patients with AIDS
DesignOpen study
Type of publicationMedical journal
Address of author(s)UNIMED, Inc., Somerville, NJ 08876.
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Dronabinol enhancement of appetite in cancer patients

TitleDronabinol enhancement of appetite in cancer patients.
Author(s)Wadleigh R, Spaulding GM, Lumbersky B, Zimmer M, Shepard K, Plasse T.
Journal, Volume, IssueProc Am Soc Oncology 1990; 9: 331.
Major outcome(s)Dronabinol stimulated mood and appetite
IndicationAppetite loss/weight loss;CancerAbstract

Delta-9-tetrahydrocannabinol has previously been noted to enhance appetite in healthy individuals and in cancer patients. To further study this phenomenon, an open, dose- ranging study was carried out in patients with unresectable cancer. After a baseline observation period, patients were treated with dronabinol (delta-9-THC in sesame oil, Marinol, Roxane Labs, Columbus, OH) for up to six weeks at doses of 2.5 mg qd (N=8), 2.5 mg bid (N=9) or 5 mg qd (N=13); patient accrual and dose escalation are still continuing. Patients were weighed weekly; they recorded appetite before each meal and their overall mood once daily 0n 10cm visual analog scales (VAS). Five patients discontinued dronabinol because of adverse effects, although some may have been related to other medications; three discontinued because of progressive desease. Patients in all groups continued to lose weight, although the rate of weight loss decreased with therapy at all doses. Symptomatic improvement was noted in both mood and appetite, with 2.5 mg qd being a no- effect dose. For patients on study at least three weeks, the following was seen:
Group 2.5 mg qd: N=6; Mean VAS Mode=-1.5; change, Appetite: -5.4; Mean decrease in weight loss, ib/wk=1.3.
Group 2.5 mg bid: N=7; Mean VAS Mode=10.8; change, Appetite: 18; Mean decrease in weight loss, ib/wk=0.6.
Group 5 mg qd: N=9; Mean VAS Mode=1.2; change, Appetite: 8.9; Mean decrease in weight loss, ib/wk=1.7
In this open, dose-ranging study, dronabinol appeared to stimulate both mood and appetite at well tolerated doses.

 All Conditions Benefited by Medical Marijuana

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Dose(s)2.5 mg twice - 5 mg four times daily
Duration (days)42
Participants30 cancer patients.
DesignOpen study
Type of publicationMeeting abstract
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Effects of smoked marijuana on food intake and body weight

TitleEffects of smoked marijuana on food intake and body weight of humans living in a residential laboratory.
Author(s)Foltin RW, Fischman MW, Byrne MF.
Journal, Volume, IssueAppetite 1988;11(1):1-14.
Major outcome(s)Increases in body weight during periods of active marijuana smoking were greater than predicted by caloric intake alone.
IndicationAppetite loss/weight lossAbstract

Six adult male research volunteers, in two groups of three subjects each, lived in a residential laboratory for 13 days. All contact with the experimenter was through a networked computer system and subjects’ behaviors, including food intake, were continuously reported. During the first part of the day , subjects remained in their private rooms doing planned work activities, and during the remainder of the day, they were allowed to socialize. Two cigarettes containing active marijuana (2-3% Delta-9-THC) or placebo were smoked during both the private work period and the period of access to social activities. Smoked active marijuana significantly increased total daily caloric intake by 40%. Increased food intake was evident during both private and social periods. The increase in caloric intake was due to an increased consumption of snack foods as a consequence of an increase in the number of snacking occasions. There was no significant change in caloric consumption during meals. The principal increase within the category of snack foods was in the intake of sweet solid items, e.g., candy bars, compared to sweet fluid, e.g., soda, or savory solid items, e.g., potato chips. Increases in body weight during periods of active marijuana smoking were greater than predicted by caloric intake alone

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Behavioral analysis of marijuana effects on food intake in humans

TitleBehavioral analysis of marijuana effects on food intake in humans.
Author(s)Foltin RW, Fishman MW, Brady JV.
Journal, Volume, IssuePharmacology, Biochemistry and Behavior 1986;25:577-582.
Major outcome(s)The administration of two or three active marijuana cigarettes during the social access period increased average daily caloric intake.
IndicationAppetite loss/weight lossAbstract

Nine male research volunteers, in three groups of three subjects each, resided in a residential laboratory for up to 25 days. All contact with the experimenter was through a networked computer system and subjects’ behaviors including food intake were continuously recorded. Subjects brought their own activities such as model-making, and these in combination with those provided by the laboratory resulted in rich behavior repertoires. During the first part of the day, subjects remained in their private rooms doing planned work activities, and during the remainder of the day, they were allowed to socialize. Cigarettes containing active marijuana (1.84% THC) or placebo were smoked prior to the private work period and during the social access period. A single active marijuana cigarette prior to the private work period had no effect on food intake. The administration of two or three active marijuana cigarettes during the social access period increased average daily caloric intake. The increased intake was due to an augmentation of calories consumed as between-meal snack items rather than an increase in meal size per

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Duration (days)up to 25
ParticipantsNine male research volunteers
DesignControlled study
Type of publicationMedical journal
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Cancer related anorexia cachexia syndrome

Strasser F, Luftner D, Possinger K, Ernst G, Ruhstaller T, Meissner W, Ko YD, Schnelle M, Reif M, Cerny


Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. [Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't]
J Clin Oncol 2006 Jul 20; 24(21):3394-400.

PURPOSE: To compare the effects of cannabis extract (CE), delta-9-tetrahydrocannabinol (THC), and placebo (PL) on appetite and quality of life (QOL) in patients with cancer-related anorexia-cachexia syndrome (CACS).


PATIENTS AND METHODS: Adult patients with advanced cancer, CACS, weight loss (> or = 5% over 6 months), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2 were randomly assigned (2:2:1) to receive CE (standardized for 2.5 mg THC and 1 mg cannabidiol) or THC (2.5 mg) or PL orally, twice daily for 6 weeks. Appetite, mood, and nausea were monitored daily with a visual analog scale (VAS); QOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (composite score: questions 29 and 30). Cannabinoid-related toxicity was assessed every 2 weeks.


RESULTS: Of 289 patients screened, 243 were randomly assigned and 164 (CE, 66 of 95 patients; THC, 65 of 100 patients; and PL, 33 of 48 patients) completed treatment. At baseline, groups were comparable for age (mean, 61 years), sex (54% men), weight loss (32% > or = 10%), PS (13% ECOG = 2), antineoplastic treatment (50%), appetite (mean VAS score, 31/100 mm), and QOL (mean score, 30/100). Intent-to-treat analysis showed no significant differences between the three arms for appetite, QOL, or cannabinoid-related toxicity. Increased appetite was reported by 73%, 58%, and 69% of patients receiving CE, THC, or PL, respectively. An independent data review board recommended termination of recruitment because of insufficient differences between study arms.


CONCLUSION: CE at the oral dose administered was well tolerated by these patients with CACS. No differences in patients' appetite or QOL were found either between CE, THC, and PL or between CE and THC at the dosages investigated.


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THC effective in appetite and weight loss in severe lung disease (COPD)

Patients with the severe lung disease COPD (chronic obstructive pulmonary disease) often suffer from appetite loss and cachexia (weight loss) resulting in reduced general well-being and early mortality. In an open clinical study THC improved appetite and well-being and resulted in weight gain.

18 COPD patients aged 49 to 81 years with a mean body weight of 48.5 kg were included in the study under the guidance of Dr. Karl-Christian Bergmann at the Clinic for Allergies and Asthma in Bad Lippspringe, Germany. In the six months before entering the clinic 7 participants had a constant body weight and 11 lost 2.3 kg on average.

They received 3.3-4.2 mg THC two times daily as oily drops delivered by THC Pharm, half an hour before breakfast and dinner. Mean treatment duration was 16 days resulting in a considerable improvement of appetite, general well-being and functional performance (36 per cent mean increase in walking distance) and an average gain in body weight of 1.5 kg, which is much regarding the short treatment period. Side effects were mild.

(Source: Lecture by K-C Bergmann on 17 March 2005 at the Meeting of the German Society of Pulmonology in Berlin)


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Machinery Of The 'Marijuana Munchies'

ScienceDaily (Dec. 26, 2005) — Marijuana--or more specifically its active ingredient, tetrahydrocannabinol--has a well-documented tendency to stimulate hunger. And while scientists have traced this property to cannabinoid receptors in the brain, they have had little understanding of the neural circuitry underlying this effect

Understanding this circuitry has important practical implications because blocking the cannabinoid receptor, CB1, offers a promising approach to treating obesity. One such compound, rimonabant (trade name AcompliaTM) is already undergoing clinical testing.

In an article in the December 22, 2005, issue of Neuron, Young-Hwan Jo and colleagues report how the circuitry of CB1 is integrated with signaling by the appetite-suppressing hormone leptin. The CB1 receptor is normally triggered by natural regulatory molecules, called endocannabinoids.

In their studies, the researchers concentrated on the lateral hypothalamus (LH) of the brain, known to be a center of control of food intake. Their studies involved detailed electrophysiological measurements of the effects of specific neurons that they had identified in previous studies as being important in endocannabinoid signaling.

Their studies revealed that activation of CB1 receptors, as by endocannabinoid molecules, induced these neurons to be rendered more excitable by a mechanism called "depolarization-induced suppression of inhibition" (DSI).

What's more, they found that leptin inhibits DSI. However, they found that leptin did not interfere with the CB1 receptors themselves. Rather, leptin "short-circuits" the endocannabinoid effects by inhibiting pore-like channels in the neurons that regulate the flow of calcium into the neurons. Such calcium is necessary for the synthesis of endocannabinoids.

In further studies of mice genetically altered to be leptin deficient, the researchers found the DSI to be more prolonged than in normal mice. Thus, they said, the findings "implicate this mechanism for leptin receptor/endocannabinoid signaling in contributing to the maintenance of weight balance...." The researchers also included that "upregulation of endocannabinoid signaling in the LH may explain, at least in part, the increased body weight consistent with a prior report of elevated endocannabinoids" in such leptin-deficient mice.

The researchers concluded that their findings "are consistent with the hypothesis that the integration of endocannabinoid and leptin signaling regulates the excitability of neurons on appetite-related circuits."

They also wrote that "the cellular mechanisms of recently developed antiobesity drugs, such as rimonabant, may include decreased endocannabinoid signaling and hence decreased excitability of LH circuits related to appetite, even in the context of leptin insufficiency or resistance."

The researchers included Young-Hwan Jo, Ying-Jiun J. Chen, Streamson C. Chua, Jr., David A. Talmage and Lorna W. Role of Columbia University in New York, New York. This work was supported by NS22061 and a NARSAD Grable Distinguished Investigator award to L.W.R.; by CA79737 to D.A.T.; by DK57621 to S.C.C.; and by an award from the New York Obesity Research Center to Y.-H.J.

Jo et al.: "Integration Of Endocannabinoid and Leptin Signaling in an Appetite-Related Neural Circuit." Publishing in Neuron, Vol. 48, 1055-1066, December 22, 2005, DOI 10.1016/j.neuron.2005.10.021 www.neuron.org.


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Factors influencing the aggressiveness elicited by marihuana in food-deprived rats

E. A. Carlini, A. Hamaoui, and Regina M. W. Märtz

1. Aggressive behaviour was elicited in rats that had been deprived of food for 20 h daily (starved), by chronic administration of Cannabis sativa extract or (-)-Δ9-trans-tetrahydrocannabinol.
2. The influence of intraperitoneal (i.p.) or oral glucose administration, cold environment, acidosis, and corn, and protein-free diets on this aggressiveness was studied.
3. Intraperitoneal injections of glucose (100-1,600 mg/kg) did not alter the aggressiveness induced by marihuana in starved rats; glucose given orally, however, blocked this behaviour.
4. Low temperature (14° C) strongly potentiated the aggressive behaviour induced by marihuana in the starved rats.
5. Lactic acid in doses capable of potentiating thiopental anaesthesia, failed to alter the marihuana-aggressiveness of starved rats or to facilitate this effect of marihuana in rats fed ad libitum. The same negative results were obtained with ammonium chloride.
6. In rats fed ad libitum with protein-free or corn diets, marihuana administered chronically did not elicit aggressive behaviour. However, aggressiveness appeared when rats were fed for only 2 h daily on those diets.
7. The results suggest that the stress of hunger (and not hypoglycaemia, acidosis or lack of specific nutrients due to starvation) is the factor that facilitates the development of aggressive behaviour by chronic administration of marihuana.

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Immunoactive cannabinoids: Therapeutic prospects for marijuana constituents

Stephen E. Straus*
National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892-2182
*E-mail: sstraus@nih.gov.
Marijuana, the common name for Cannabis sativa, is a widely distributed hemp plant whose dried flowering tops and leaves have been used for medicinal purposes for 12,000 years by some estimates (1). The article by Malfait et al. (2) in this issue of PNAS is relevant to the question of whether such traditional uses of marijuana could be clinically justifiable today.
Contemporary discussions of the medical value of marijuana must be undertaken within a larger cultural, legal, and political context (Workshop on the Medical Utility of Marijuana, National Institutes of Health, http://www.nih. gov/news/medmarijuana/MedicalMarijuana.htm). The perceived behavioral and addictive effects of marijuana led to its prohibition from nonmedical uses by most states, taxation at the federal level, and eventual removal from the U.S. Pharmacopoeia in the 1930s and 1940s. Nonetheless, smoking of marijuana cigarettes continued and became the recreational drug practice of choice as well as a virtual rite of passage for young people during the Vietnam era. Some people who suffered chronic debilitating illnesses observed that marijuana eased some of their symptoms. A movement grew to redefine marijuana as a neglected, but valuable, therapeutic tool. Today, that movement has been subsumed under a more general advocacy for a whole spectrum of complementary and alternative health approaches (3).
Complementary and alternative medicine entails the use of unconventional diagnostic, preventative, and therapeutic approaches including acupuncture, chiropractic manipulation, homeopathy, and magnets, few of which have been tested according to rigorous scientific standards. Herbal and other botanical products are key components of many alternative health approaches. Numerous preparations are marketed in the United States as nutritional supplements with such promises as combating fatigue, restoring mental balance, warding off respiratory infections, losing weight, and relieving the pains of arthritis.
Were botanical products merely inert food supplements or condiments, there would be little concern over their use. But the very discoveries that yielded aspirin, digoxin, vincristine, taxol, and many other valuable plant-based drugs informed us as well of their potential for harm. Despite the common belief that natural substances must be healthful, the media and scientific literature today are rife with reports of serious adverse effects of particular botanical supplements and unexpected interactions between some supplements and proprietary drugs. Thus, the public need for definitive preclinical and clinical testing of botanicals and other unconventional healing approaches led to the creation in 1999 of the National Center for Complementary and Alternative Medicine at the National Institutes of Health.
With regard to marijuana, there are data to indicate that the plant, or at least some of its constituents, conveys some clinical benefits, but a number of risks as well. Comprehensive reviews of the medical utility of marijuana were undertaken by a National Institutes of Health workshop in 1997 and by the Institute of Medicine in 1999 (http: //www.nih.gov/news/medmarijuana/MedicalMarijuana.htm and ref. 4). These reviews concluded that smoking marijuana reduces intraocular pressure in glaucoma and is claimed to ameliorate pain, cachexia, nausea, and other debilitating conditions. Unfortunately, large controlled trials have not been conducted to support the majority of such claims. Moreover, there are better, well-defined treatments for virtually all such indications.
Far more certain than reports of the benefits of marijuana smoking, however, are the health risks it imposes. Studies have described its adverse psychological, cardiovascular, and pulmonary effects, and even raised the specter of an increased risk of cancer (5, 6).
In contrast to the incomplete state of the science regarding use of the plant itself, the identity, pharmacology, and clinical effects of several of marijuana's constituents are relatively well characterized (7, 8). Marijuana contains more than 60 distinct cannabinoids, of which a series of tetrahydrocannabinols (THC) and their metabolites are the primary psychoactive ingredients and best-known components (Fig. (Fig.1).1). Δ9-THC alleviates the nausea associated with cancer chemotherapy and AIDS wasting and is available for these indications as the prescription drug dronabinol. Even the nonpsychoactive cannabinoids have been shown to have cellular and physiologic effects that could prove of clinical value.
Figure 1
Figure 1
The chemical structures of Δ9-THC and cannabidiol.
The paper by Malfait et al. (2) summarizes in vitro and in vivo immunological studies of the marijuana constituent cannabidiol (CBD; Fig. Fig.1)1) and its potential effects in the treatment of arthritis (1). Using a murine model in which arthritis is induced by immunization with type II collagen, the authors show that CBD blocks the inflammatory infiltrate and progression of joint damage. CBD appears effective both orally and intraperitoneally, but with a rather sharp dose-response peak, above or below which efficacy is less evident. A series of ex vivo studies indicate that CBD attenuates the oxidative burst in granulocytes, lymphocyte proliferation, and the release of proinflammatory cytokines.
Numerous prior studies of marijuana itself, unfractionated marijuana extracts, and individual cannabinoids revealed that they manifest a wide range of immunologic effects, both in vitro and in vivo, in animals as well as in human subjects (reviewed in ref. 9). Generally suppressive effects on T cell, B cell, macrophage, natural killer cell, and neutrophil functions have been described. Proliferation is impaired, as is release of selected cytokines and chemokines, but the findings differ by cell type, experimental conditions, and especially the concentration of the cannabinoids examined. The effects are sufficient, nonetheless, to impair host responses to animal challenges with several viral and bacterial pathogens. Moreover, the psychoactive potential of the molecule does not correlate with its immunological effects. For example, both THC and CBD were shown to inhibit release of IFN-γ and tumor necrosis factor α from cultured human peripheral blood mononuclear cells (10, 11). In some assays, the effects by one paralleled the other; in others, CBD was more potent. Importantly, the dose–response for either substance was complex, being stimulatory at concentrations of 0.01–0.1 μg/ml, the range of serum levels detected in marijuana smokers, but strongly inhibitory at 0.5–20 μg/ml. Given the tight peak response to CBD observed in the present report and its still undefined pharmacokinetics, it might be difficult to develop CBD into a useful anti-inflammatory or immunosuppressive drug.
Another issue that bears on the potential therapeutic utility of CBD, or any cannabinoid designed for prolonged use, is its toxicity, an issue that was not addressed by Malfait et al. (2). In addition to adverse effects like tremors, convulsions (12), and embryotoxicity (13) observed in formal animal studies, there are effects associated with its intended use, such as the suppression of inflammatory cytokine responses. Early experiences with the anti-tumor necrosis factor agents infliximab and etanercept revealed an increased incidence of intercurrent infections (14). Their long-term effects on dormant infections with mycobacteria or other intracellular pathogens are not known. An increased risk of lymphomas has been postulated as well (15).
Regardless of its eventual utility and safety, CBD is a potential lead to new classes of agents that would interfere with inflammatory pathways. Although one could only speculate as to why a common weed like Cannabis would evolve to contain THC and CBD, we do know something of the cellular mechanisms by which it acts on the mammalian immune and nervous systems. Two related cannabinoid receptors have been described: CB1 and CB2 (Table (Table1;1; refs. 16 and 17). They are both widely distributed G-coupled protein receptors. High densities of CB1 are found in the cortex, limbic system, and hippocampus, where endogenous ligands like anandamide serve as neurotransmitters. CB2 also is expressed in the brain, but is found in relatively higher concentrations than CB1 in various lymphocyte subpopulations, especially B cells. That CBD does not bind to either CB1 or CB2 implies that additional receptors remain to be discovered. The evolving work suggests that the differential expression of cannabinoid receptors, and the particular endogenous ligands accessible to them in specific tissues, constitute a rich regulatory network (18, 19).
Table 1
Table 1
The distribution and ligand affinitives of cannabinoid receptors
Many proponents of complementary and alternative medicine find the discovery of neuro-immune effector molecules, such as the cannabinoid receptors and their endogenous ligands, to be an exciting validation of their traditional beliefs about the unity of mind and body. They extol the proverbial wisdom of nature in providing medicinal plants whose components can affect human cells through evolutionarily conserved biochemical mechanisms. They believe, as well, that the multiplicity of related constituents in medicinal plants act collectively to enhance overall beneficial effects while tempering adverse ones.
It is conceivable that marijuana contains a series of cannabinoids that, in the aggregate, could alleviate arthritis as implied in the present report (2), yet remain well tolerated. Remarkably, the claim that marijuana does so also was made 4,000 years ago by the Chinese emperor Shen-nung whose pharmacobotanical compendium, the Pen-ts'ao Ching, concluded that cannabis “undoes rheumatism (cited in ref. 20). These are ideas that are now susceptible to critical scrutiny through controlled trials in which purified plant constituents are compared, alone and in combination, with whole-plant products.
See companion article on page 9561.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.180314297.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.180314297
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Natural Pot-Like Compound Could Fight Obesity


A study in the Proceedings of the National Academy of Sciences finds that endocannabinoids, compounds naturally found in the body related to pot's active ingredient, could inform the effort to control appetite. Cynthia Graber reports



Could there be a substance that both gives us the munchies and can help combat obesity? There may indeed be, according to research published in the Proceedings of the National Academy of Sciences.

The Monell Center in Pennsylvania partnered with Kyushu University in Japan to study compounds called endocannabinoids. These occur naturally in our body and are similar to THC, the compound primarily responsible for marijuana’s psychoactive effects.



Researchers studied endocannabinoids in mice, and they say that the chemicals have a one-two punch—in your brain, they increase your appetite. And on your tongue, they enhance the response to sweet flavors. The compounds had no effect on salty, sour, bitter or umami tasting.



It turns out that sweetness receptors are present in the same cells as cannabinoid receptors on our tongues. But how could such an effect contribute to combating obesity? According to the scientists, there are similar sweet receptors in hormone-producing cells in the intestine and pancreas. There, they affect metabolism and the absorption of nutrients. Scientists say that if endocannabinoids also act on those receptors it could lead to new compounds to moderate metabolism. Which might stop the development of the pot belly.

—Cynthia Graber

 December 29, 2009


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Dronabinol and marijuana in HIV-positive marijuana smokers: caloric intake, mood, and sleep

Margaret Haney et al, "Dronabinol and Marijuana in HIV-Positive Marijuana Smokers,

Caloric Intake, Mood, and Sleep," Journal of Acquired Immune Deficiency Syndromes 45, issue 5 (August 15, 2007): 545-554.



This clinical trial found that both smoked marijuana and the THC pill (Marinol, known generically as dronabinol) are effective at increasing caloric intake and weight among HIV-positive patients, with no effect on cognitive performance. Strikingly, however, it took eight times the standard dose of Marinol to approximate the effect of weak (3.9% THC) marijuana, and even at that dose, natural marijuana outperformed Marinol in some measurements.



The full study is available for free download here: http://journals.lww.com/jaids/Fulltext/2007/08150/Dronabinol_and_Marijuana_in_HIV_Positive_Marijuana.9.aspx?desktopMode=true


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