Cannabis Health Science Studies Index

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HIV and AIDS & Cannabis studies completed

Overview

The Human Immunodeficiency Virus (HIV) is a lentivirus that causes the acquired immunodeficiency syndrome, a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive.
*Lentivirus (lente-, Latin for "slow") is a genus of viruses of the Retroviridae family,

Science & Research

1991 - Study - Recent clinical experience with dronabinol.

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

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

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

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

2001 - Study - Therapeutic Aspects of Cannabis and Cannabinoids.

2003 - Study - Short-term effects of cannabinoids in patients with HIV-1 infection.

2003 - Study - Therapeutic potential of cannabinoids in CNS disease.

2003 - Patent - US Patent 6630507 - Cannabinoids as antioxidants and neuroprotectants.

2004 - News - Marijuana Use Does Not Accelerate HIV Infection.

2005 - Study - Cannabis: Use in HIV for Pain and Other Medical Symptoms.

2005 - Study - Smoked cannabis therapy for HIV-related painful peripheral neuropathy.

2005 - Study - Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation.

2007 - Study - Marijuana as therapy for people living with HIV/AIDS: Social and health aspects.

2007 - Study - Marijuana and AIDS: A Four-Year Study.

2007 - Study ~ Smoked cannabis therapy for HIV-related painful peripheral neuropathy.

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

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

2007 - Study - Cannabis in painful HIV-associated sensory neuropathy.

2007 - Study ~ Cannabis: Use in HIV for Pain and Other Medical Symptoms.

2007 - Study ~ The endocannabinoid system in targeting inflammatory neurodegenerative diseases.

2007 - News ~ Cannabis may be safe and effective for HIV-related neuropathic pain.

2007 - News ~ Smoked Cannabis Reduces Foot Pain Associated With HIV In Placebo Trial.

2007 - News ~ Marijuana gives relief from chronic pain for AIDS sufferers.

2007 - News ~ Marijuana, Very Efficient in Cutting Off HIV Related Nerve Pain.

2008 - Study - Denbinobin... inhibits HIV-1 replication through an NF-kappaB-dependent pathway.

2008 - Study ~ Recreational Drug Use and T Lymphocyte Subpopulations in HIV-uninfected and HIV-infected Men.

2008 - Study ~ Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial.

2008 - Study ~ Cannabinoid CB2 receptors in human brain inflammation.

2008 - Study ~ Cannabinoids Inhibit HIV-1 Gp120-Mediated Insults in Brain Microvascular Endothelial Cells.

2009 - Study ~ Recreational Drug Use and Risk of Kaposi's Sarcoma in HIV- and HHV-8-Coinfected Homosexual Men.

2009 - News ~ Marijuana Rivals Mainstream Drugs For Alleviating HIV/AIDS Symptoms.

2009 - News ~ Medical Marijuana and AIDS Related Illness.

2009 - News - Marijuana Effectiveness as an HIV Self-Care Strategy.

Marijuana as therapy for people living with HIV/AIDS: Social and health aspects

Fogarty A, Rawstorne P, Prestage G, Crawford J, Grierson J, Kippax S

 AIDS Care 2007 Feb; 19(2):295-301.

Therapeutic use of marijuana has emerged as an important issue for people living with cancer, HIV/AIDS and multiple sclerosis. This paper examines therapeutic use of marijuana in the Positive Health cohort study, a longitudinal cohort study of men and women living with HIV/AIDS in NSW and Victoria, Australia. Factors that distinguish therapeutic use of marijuana from recreational use were assessed by comparisons on a range of social and health-related variables.

The results show that among 408 participants, 59.8% reported some use of marijuana in the past six months. Of those participants (n=244), 55.7% reported recreational use only of marijuana and 44.3% report mixed use of marijuana for therapeutic and recreational purposes. Multivariate logistic regression analysis showed that participants who used marijuana for therapeutic purposes were significantly more likely than recreational-only users to have used other complementary or alternative therapies, experienced HIV/AIDS-related illness or other illnesses in the past 12 months, had higher CD4/T-cell counts, had lower incomes, be younger in age and less likely to have had a casual partner in the six months prior to interview.

These results show that a substantial proportion of people living with HIV/AIDS (PLWHA) use marijuana for therapeutic purposes, despite considerable legal barriers, suggesting marijuana represents another option in their health management. Rather than solely using marijuana in response to illness, the experience of illness may influence a person's understanding of their marijuana use, so that they come to understand it as therapeutic. Further research might consider possible interactions between cannabinoids and antiretroviral treatments, potential use of oral THC and the difficulties faced by clinicians and PLWHA in discussing marijuana in the current legal context.

More from this journal AIDS care[AIDS Care]

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Cannabis: Use in HIV for Pain and Other Medical Symptoms

 
J Pain Symptom Manage. 2005 Apr;29(4):358-67.

Source

Magill Department of Anesthesia, Imperial College London, United Kingdom.

Abstract

Despite the major benefits of antiretroviral therapy on survival during HIV infection, there is an increasing need to manage symptoms and side effects during long-term drug therapy. Cannabis has been reported anecdotally as being beneficial for a number of common symptoms and complications in HIV infections, for example, poor appetite and neuropathy. This study aimed to investigate symptom management with cannabis.

Following Ethics Committee approval, HIV-positive individuals attending a large clinic were recruited into an anonymous cross-sectional questionnaire study. Up to one-third (27%, 143/523) reported using cannabis for treating symptoms.

Patients reported improved appetite (97%), muscle pain (94%), nausea (93%), anxiety (93%), nerve pain (90%), depression (86%), and paresthesia (85%). Many cannabis users (47%) reported associated memory deterioration. Symptom control using cannabis is widespread in HIV outpatients. A large number of patients reported that cannabis improved symptom control.

 

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Marijuana and AIDS: A Four-Year Study

Patients reported reduced levels of pain, nausea and insomnia--and increased appetite.

by David Jay Brown, Kenneth Michael Smuland, and Valerie Corral
The Wo/Men’s Alliance for Medical Marijuana (WAMM) is a cultivation collective in Northern California with approximately 150-175 patient-members, who suffer from a range of debilitating illnesses, including cancer, AIDS, epilepsy, multiple sclerosis, and glaucoma.

In 1993 the authors undertook to assess the medical effectiveness of marijuana on WAMM’s AIDS patients.


Previous studies have demonstrated marijuana’s usefulness in reducing nausea and vomiting, stimulating appetite and promoting weight gain2 and diminishing intra-ocular pressure from glaucoma . There is also evidence that marijuana reduces muscle spasticity from spinal cord injuries and multiple sclerosis, and diminishes tremors in multiple sclerosis.


WAMM developed an assessment form —known as an analog— for the symptoms that marijuana is reputed to alleviate. Weekly reports were collected from members. All of the patients studied had AIDS. The symptoms assessed were pain, nausea, insomnia, and lack of appetite.

Method
This study ran from June 1993 through December 1997. Data were collected by means of analogs given by WAMM to each of its patient-members with their weekly supply of medical marijuana. Our analog was adapted from one used in Charles Grob’s MDMA studies with pancreatic cancer patients7, revised by AIDS patients to incorporate their symptoms. The patients were asked to mark on the analogs how they felt before and after they smoked marijuana with respect to each of the applicable symptoms.
The scale on the analogs ranged from zero to 10, with 10 being the highest intensity level of symptom or physical-emotional state (pain, nausea, insomnia, and appetite.)

Results
There were a total of 264 subjects with AIDS in the study—44 women and 220 men—however not all of the symptoms measured on the analogs applied to all of the subjects.
For 29 women the medium average level of pain reported prior to using marijuana was 6.5. After using the medication the medium average level of pain dropped to 3.2. The result of the two-tailed t-test P(T<=t) was 1.45E-08.


For 37 women the medium average level of nausea reported prior to using marijuana was 5.2. After using the medication the medium average level of nausea dropped to 3.1. The result of the two-tailed t-test P(T<=t) was 0.003.


For 44 women the medium average appetite level reported prior to using marijuana was 2.3. After using the medication the medium average appetite level rose to 6.3. The result of the two-tailed t-test P(T<=t) was 8.33E-15.


For 29 women the medium average level of insomnia reported prior to using marijuana was 7.2. After using the medication the medium average level dropped to 3.4. The result of the two-tailed t-test P(T<=t) was 8.33E-15.


For 175 men the medium average level of pain reported prior to using marijuana was 5.9. After using the medication the medium average pain level dropped to 2.4. The result of the two-tailed t-test P(T<=t) was 4.3E-30.


For 203 men the medium average level of nausea reported prior to using marijuana was 5.4. After using the medication the medium average level of nausea dropped to 2.8, The result of the two-tailed t-test P(T<=t) was 3.25E-25.


For 220 men the medium average appetite level reported prior to using marijuana was 3.3. After using the medication the medium average appetite level rose to 6.2. The result of the two-tailed t-test P(T<=t) was 1.72E-33.

Discussion
This study indicates that these AIDS patients believed that they experienced significantly less pain, nausea, and insomnia, and had much greater appetites after using marijuana.

In this study we were testing the null hypothesis that AIDS patients would not experience any significant difference in their symptoms before and after using marijuana. In every case our results indicated a rejection of the null hypothesis with a statistical significance greater than 0.01. This is consistent with previous studies and claims, which suggest that marijuana can help reduce pain and nausea, improve appetites, and help people sleep better.

Improving the quality of an AIDS patient’s life increases the probability that person will stick with other lifesaving medical procedures

For someone with AIDS—a condition that requires a lifetime of chemotherapy—these improvements can mean the difference between life and death. Improving the quality of an AIDS patient’s life increases the probability that that person will stick with other lifesaving medical procedures, some of which have extremely uncomfortable side-effects. In addition to reducing the side-effects from other types of medication, marijuana can serve as a powerful appetite-stimulant for those suffering from the AIDS Wasting Syndrome.

The subjective nature of analog responses inherently raises questions of reliability. In this study a possible source of bias may stem from a tendency for marijuana users to exaggerate how much better they felt after using the medication. This seems unlikely, however, as they would have little motivation for doing so.


Although it is beyond our current ability to know with any certainty how much bias influenced our data, it is evident that many AIDS patients report significant benefits from using marijuana. Because of this, and the lack of any serious side-effects, marijuana appears to be a powerful medical tool for dealing with the serious consequences of AIDS.

WAMM is conducting ongoing research into the effects of marijuana on patients with AIDS and other illnesses, including cancer, epilepsy, multiple sclerosis, and glaucoma. Research is required to determine the effects exerted by different strains of the marijuana plant, and the efficacy of various delivery systems (vaporizing, eating, tinctures, etc.)

Acknowledgments
The authors wish to thank all those who took part in this study.
WAMM is a collective run entirely by patients and caregivers. It relies on tax-deductible donations to continue its operation, and the valuable research its doing. For reprint requests and correspondence contact:
WAMM
309 Cedar ST # 39
Santa Cruz, California 95060
(831) 425-0580


References
1, Chang, A.E. et al., “Delta-Nine-Tetrahydrocannabinol as an Antiemetic in Cancer Patients Receiving High-Dose Methotrexate: A Prospective Randomized Evaluation,” Annals of Internal Medicine 91: 819-24 (1979).
Orr, L.E. et al., “Antiemetic Effect of Tetrahydrocannabinol Compared with Placebo and Prochlorperazine in Chemotherapy-Associated Nausea and Emesis,” Archives of Internal Medicine 140: 1431-33 (1980).
Vinciguerra, V. et al., “Inhalation of Marijuana as an Antiemetic for Cancer Chemotherapy,” New York State Journal of Medicine 85: 525-27 (1988).
2. Foltin, R.W. et al., “Effects of Smoked Marijuana on Food Intake and Body Weight of Humans Living in Residential Laboratory,” Appetite 11: 1-14 (1988).
Plasse, T.F. et al., “Recent Clinical Experience with Dronabinol,” Pharmacology Biochemistry and Behavior 40: 695-700 (1991).
Gorter, R. et al., “Dronabinol Effects on Weight in Patients with HIV Infection,” AIDS 6: 127-38 (1992).
3. Crawford, W.J. and Merritt, J.C., “Effects of Tetrahydrocannabinol on Arterial and Intraocular Hypertension,” International Journal of Clinical Pharmacology and Biopharmaceutics 17: 191-96 (1979).
Merritt, J.C. et al., “Effects of Marijuana on Intraocular and Blood Pressure in Glaucoma,” Ophthalmology 87:222-28 (1980).
4. Malec, J. et al., “Cannabis Effect on Spasticity in Spinal Cord Injury,” Archives of Physical and Medical Rehabilitation 63: 116-18 (1982).
Hanigan, W.C. et al., “The Effect of Delta-9-THC on Human Spasticity,” Clinical Pharmacology and Therapeutics 39: 198 (1986).
5. Ungerleider, J.T. et al., “Delta-9 THC in the Treatment of Spasticity Associated with Multiple Sclerosis,” Advances in Alcohol and Substance Abuse 7: 39-50 (1987).
Meinck, H.M. et al., “Effects of Cannabinoids on Spasticity and Ataxia in Multiple Sclerosis,” Journal of Neurology 236: 120-22 (1989).
6. Clifford, D.B., “Tetrahydrocannabinol for Tremor in Multiple Sclerosis,” Annals of Neurology 13: 669-71 (1983).
7. Grob, C. et al., “Analgesic safety and efficacy of MDMA in modification of pain and distress of end-stage cancer,” unpublished (2004).

 

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Therapeutic Aspects of Cannabis and Cannabinoids

 
The British Journal of Psychiatry
© 2001 The Royal College of Psychiatrists

Volume 178             February 2001             pp 107-115

[Substance Misuse Papers]

ROBSON, PHILIP

PHILIP ROBSON, FRCPsych, Consultant Psychiatrist and Senior Clinical Lecturer, Warneford Hospital, Oxford OX3 7JX
See editorial, p. 98, this issue.
(First received 22 July 1999, final revision 14 March 2000, accepted 15 March 2000)
 Abstract

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.

HISTORY OF THERAPEUTIC USE
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.

CANNABINOID PHARMACOLOGY RELEVANT TO THERAPEUTICS
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.

CLINICAL APPLICATIONS
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).
Graphic

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.
Graphic

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.

Pain
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).


Graphic

Table 3 Human randomised controlled trials (RCTs): pain 

Raised intra-ocular pressure


Graphic

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.


Graphic

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
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.

Asthma
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.

 

DISCUSSION
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.

CLINICAL IMPLICATIONS
* 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.

LIMITATIONS
* 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.

ACKNOWLEDGEMENT
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. 
APPENDIX
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.

Systemic drugs (acctazolamide, dichlorphenamide) can cause hypokalaemia, appetite suppression, paraesthesiae, drowsiness, depression, rashes and, rarely, bone marrow suppression. [Context Link]

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Marijuana Effectiveness as an HIV Self-Care Strategy

  1. Inge B. Corless
  2. Teri Lindgre
  3. William Holzemer
  4. Linda Robinson
  5. Shahnaz Moezzi
  6. Kenn Kirksey
  7. Christopher Coleman
  8. Yun-Fang Tsai
  9. Lucille Sanzero Eller
  10. Mary Jane Hamilto
  11. Elizabeth F. Sefcik
  12. Gladys E. Canaval
  13. Marta Rivero Mendez
  14. Jeanne K. Kemppainen
  15. Eli H. Bunch
  16. Patrice K. Nicholas
  17. Kathleen M. Nokes
  18. Pamela Dole
  19. Nancy Reynolds

+ Author Affiliations

  1. MGH Institute of Health Professions, School of nursing, Boston, Massachusetts, [email protected]
  2. University of California-San Francisco, San Francisco, Calfifornia
  3. University of California-San Francisco, San Francisco, Calfifornia
  4. University of San Diego, San Diego, California
  5. University of Utah
  6. Seton Family of Hospitals, Austin, Texas
  7. University of Pennsylvania
  8. Chang Gung University, Taiwan
  9. 9Rutgers University
  10. Texas A&M University
  11. Texas A&M University
  12. Universidad del Valle Cali, Colombia
  13. 13University of Puerto Rico
  14. University of North Carolina-Wilmington
  15. University of Oslo
  16. Brigham and Women's Hospital, Boston, Massachusettes
  17. Hunter College City University of New York
  18. New York, New York
  19. Yale University

Abstract

Persons living with HIV/AIDS use self-care for symptom management.

This study assesses the use of marijuana as a symptom management approach for six common symptoms for persons living with HIV/AIDS--anxiety, depression, fatigue, diarrhea, nausea, and peripheral neuropathy.

This sub-analysis of the efficacy of a symptom management manual encompasses the experiences of participants from sites in the U.S., Africa, and Puerto Rico. Baseline data are analyzed to examine differences in the use and efficacy of marijuana as compared with prescribed and over-the-counter medications as well as the impact on adherence and quality of life.

 

 

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

TitleDronabinol and marijuana in HIV-positive marijuana smokers: caloric intake, mood, and sleep.
Author(s)Haney M, Gunderson EW, Rabkin J, Hart CL, Vosburg SK, Comer SD, Foltin RW
Journal, Volume, IssueJ Acquir Immune Defic Syndr 2007;45(5):545-554.
Major outcome(s)THC and cannabis caused an increase in caloric intake and weight
 
IndicationAppetite loss/weight loss;HIV/AIDSAbstract
MedicationCannabis;Delta-9-THC

OBJECTIVES

All Conditions Benefited by
Medical Marijuana


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Route(s)Inhalation;Oral
Dose(s)up to 10 mg THC
Duration (days)32
Participants10 HIV-positive cannabis users
DesignControlled study
Type of publicationMedical journal
Address of author(s)From the *Division on Substance Abuse, New York State Psychiatric Institute, and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY; and †Department of Psychology, Columbia University, New York, NY.
Full text

Smoked cannabis therapy for HIV-related painful peripheral neuropathy

TitleSmoked cannabis therapy for HIV-related painful peripheral neuropathy: results of a randomized, placebo-controlled clinical trial.
Author(s)Abrams DI, Jay CA, Vizoso H, Shade SB, Reda H, Press S, Kelly ME, Rowbotham M, Petersen K
Journal, Volume, IssueAbstract, IACM 3rd Conference on Cannabinoids in Medicine, September 9-10, 2005, Leiden
Major outcome(s)Smoked cannabis is effective in reducing HIV-related neuropathic pain
 
IndicationHIV/AIDS;PainAbstract
MedicationCannabis

INTRODUCTION: There is significant evidence that cannabinoids may be involved in the modulation of pain, especially of neuropathic origin.

HIV-related painful peripheral neuropathy is a significant medical problem with unsatisfactory treatment options.

Based on the effects of cannabinoids in pre-clinical models of neuropathic pain and anecdotal case reports, a controlled trial of smoked cannabis was conducted.

METHODS: Following a 16 patient open-label pilot proof-of-concept phase that suggested a beneficial clinical effect of seven days of smoked cannabis, a follow-on randomized, placebo-controlled trial was conducted.

Fifty participants with painful HIV-related neuropathy and baseline pain scores > 3 on a 10 point visual analog scale were admitted to the General Clinical Research Center for a 7-day inpatient stay.

Participants smoked one 3.56% tetrahydrocannabinol containing cigarette or a matching placebo three times daily for five days.

In addition to the effect of smoked cannabis on the subjects’ chronic clinical pain, the impact on an experimental heat/capsaicin pain model was also evaluated.

The primary endpoints were the reduction and relative reduction in neuropathic pain as assessed by average daily pain scores as well as the effect of smoking on acute experiemntal pain.

A 30% reduction in pain was considered to be significant for this analysis. Reduction in experimental pain was a secondary outcome measure.

RESULTS: Fifty of the 56 randomized participants (43 men, 7 women, mean age 48 years) completed the placebo-controlled trial; 25 on each arm.

Patients had an average of 6 years of neuropathic pain. In 17 cases the neuropathy was felt to be secondary to HIV alone, in 26 secondary to HIV medications and to both in 7. Baseline characteristics were well-matched across study arms.

Thirteen of the 25 patients who were randomized to marijuana cigarettes reported greater then 30% reduction in pain during the intervention phase, compared with 6 of the 25 patients receiving placebo cigarettes (p=0.04).

The pain reduction was greater in the group receiving marijuana (34%) than in the group receiving placebo (16.7%).

The marijuana group also experienced a similar significant reduction in response to the experimental pain model compared to placebo recipients.

Adverse events were not appreciated in this trial.

CONCLUSION: Smoked marijuana is effective in reducing chronic ongoing neuropathic pain as well as acute pain in the experimental pain model.

The magnitude of the response of the neuropathic pain is similar to what is seen with gabapentin, a widely used therapeutic intervention for HIV neuropathy.

 

OBJECTIVES

All Conditions Benefited by
Medical Marijuana


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Route(s)Inhalation
Dose(s) 
Duration (days)7
Participants50 HIV positives with neuropathy
DesignControlled study
Type of publicationMeeting abstract
Address of author(s)University of California San Francisco, San Francisco, California 94110, USA
Full text

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
MedicationDelta-9-THC

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.

Route(s)Oral
Dose(s) 
Duration (days)90-365
Participants117 patients with HIV/AIDS
DesignOpen study
Type of publicationMedical journal
Address of author(s)Orlando Immunology Center, Orlando, Florida, [email protected]
Full text

Cannabis in painful HIV-associated sensory neuropathy

TitleCannabis in painful HIV-associated sensory neuropathy: A randomized placebo-controlled trial.
Author(s)Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Kelly ME, Rowbotham MC, Petersen KL.
Journal, Volume, IssueNeurology 2007;68(7):515-521.
Major outcome(s)Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy.
 
IndicationHIV/AIDS;PainAbstract
MedicationCannabis

OBJECTIVE: To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model.

METHODS: Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy.

Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days.

Primary outcome measures included ratings of chronic pain and the percentage achieving >30% reduction in pain intensity.

Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model.

RESULTS: Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR = -71, -16) vs 17% (IQR = -29, 8) with placebo (p = 0.03).

Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p = 0.04).

The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p < 0.001).

Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p </= 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation.

No serious adverse events were reported.

CONCLUSION: Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy.

The findings are comparable to oral drugs used for chronic neuropathic pain.

 

OBJECTIVES

All Conditions Benefited by
Medical Marijuana

 

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Route(s)Inhalation
Dose(s)3 x cannabis cigarette
Duration (days)5
Participants50 patients with HIV-associated neuropathic pain
DesignControlled study
Type of publicationMedical journal
Address of author(s)San Francisco General Hospital, Ward 84, 995 Potrero Avenue, San Francisco, CA 94110. [email protected]
Full text

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
MedicationDelta-9-THC

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.

OBJECTIVES

All Conditions Benefited by
Medical Marijuana

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Route(s)Oral
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
Full text

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
MedicationDelta-9-THC

[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.

OBJECTIVES

All Conditions Benefited by
Medical Marijuana


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Short-term effects of cannabinoids in patients with HIV-1 infection

TitleShort-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial.
Author(s)Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT, Benowitz NL, Bredt BM, Kosel B, Aberg JA, Deeks SG, Mitchell TF, Mulligan K, Bacchetti P, McCune JM, Schambelan M
Journal, Volume, IssueAnnals of Internal Medicine 2003;139(4):258-266
Major outcome(s)Cannabis and THC had no significant effect on HI virus load and on CD4+ and CD8+ cell count
 
IndicationHIV/AIDSAbstract
MedicationCannabis;Delta-9-THC

Background: Cannabinoid use could potentially alter HIV RNA levels by two mechanisms: immune modulation or cannabinoid–protease inhibitor interactions (because both share cytochrome P-450 metabolic pathways).


Objective: To determine the short-term effects of smoked marijuana on the viral load in HIV-infected patients.
Design: Randomized, placebo-controlled, 21-day intervention trial.


Setting: The inpatient General Clinical Research Center at the San Francisco General Hospital, San Francisco, California.


Participants: 67 patients with HIV-1 infection.


Intervention: Participants were randomly assigned to a 3.95%-tetrahydrocannabinol marijuana cigarette, a 2.5-mg dronabinol (delta-9-tetrahydrocannabinol) capsule, or a placebo capsule three times daily before meals.
Measurements: HIV RNA levels, CD4+ and CD8+ cell subsets, and pharmacokinetic analyses of the protease inhibitors.


Results: 62 study participants were eligible for the primary end point (marijuana group, 20 patients; dronabinol group, 22 patients; and placebo group, 20 patients). Baseline HIV RNA level was less than 50 copies/mL for 36 participants (58%), and the median CD4+ cell count was 340 x 109 cells/L.

When adjusted for baseline variables, the estimated average effect versus placebo on change in log10 viral load from baseline to day 21 was -0.07 (95% CI, -0.30 to 0.13) for marijuana and -0.04 (CI, -0.20 to 0.14) for dronabinol. The adjusted average changes in viral load in marijuana and dronabinol relative to placebo were -15% (CI, -50% to 34%) and -8% (CI, -37% to 37%), respectively.

Neither CD4+ nor CD8+ cell counts appeared to be adversely affected by the cannabinoids.


Conclusions: Smoked and oral cannabinoids did not seem to be unsafe in people with HIV infection with respect to HIV RNA levels, CD4+ and CD8+ cell counts, or protease inhibitor levels over a 21-day treatment.

 

OBJECTIVES

All Conditions Benefited by
Medical Marijuana


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Route(s)Inhalation;Oral
Dose(s)3 x 2.5 mg THC; cannabis cigarette (3.95%THC) three times daily
Duration (days)21
Participants67 patients with HIV-1 infection
DesignControlled study
Type of publication 
Address of author(s) 
Full text

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
MedicationDelta-9-THC

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.

 

OBJECTIVES

All Conditions Benefited by
Medical Marijuana


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Route(s)Oral
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.
Full text

US Patent 6630507 - Cannabinoids as antioxidants and neuroprotectants

Patent References

2304669

(3S-4S)-7-hydroxy-Ɗ6 -tetrahydrocannabinols

Method for the production of 6,12-dihydro-6-hydroxy-cannabidiol and the use thereof for the production of trans-delta-9-tetrahydrocannabinol

NMDA-blocking pharmaceutical compositions

Neuroprotective pharmaceutical compositions of 4-phenylpinene derivatives and certain novel 4-phenylpinene compounds

Nitroxides as protectors against oxidative stress

Method of inhibiting oxidants using alkylaryl polyether alcohol polymers

NMDA-blocking pharmaceuticals
Patent #: 5521215
Issued on: 05/28/1996
Inventor: Mechoulam, et al.

Certain tetrahydrocannabinol-7-oic acid derivatives

(3S,4S)-delta-6-tetrahydrocannabinol-7-oic acids and derivatives thereof, processors for their preparation and pharmaceutical compositions containing them


Inventors

Assignee

Application

No. 09/674028 filed on 02/02/2001

US Classes:

514/454Tricyclo ring system having the hetero ring as one of the cyclos

Examiners

Primary: Weddington, Kevin E.

Attorney, Agent or Firm

International Class

A61K 31/35 (20060101)

Abstract

Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases.
 
The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention. A particular disclosed class of cannabinoids useful as neuroprotective antioxidants is formula (I) wherein the R group is independently selected from the group consisting of H, CH3, and COCH3. ##STR1##

Other References

  • Windholz et al., The Merck Index, Tenth Edition (1983) p. 241, abstract No. 1723.
  • Mechoulam et al., "A Total Synthesis of d1-Ɗ1 -Tetrahydrocannabinol, the Active Constituent of Hashish1," Journal of the American Chemical Society, 87:14:3273-3275 (1965)
  • Mechoulam et al., "Chemical Basis of Hashish Activity," Science, 18:611-612 (1970)
  • Ottersen et al., "The Crystal and Molecular Structure of Cannabidiol," Acta Chem. Scand. B 31, 9:807-812 (1977)
  • Cunha et al., "Chronic Administration of Cannabidiol to Healthy Volunteers and Epileptic Patients1," Pharmacology, 21:175-185 (1980)
  • Consroe et al., "Acute and Chronic Antiepileptic Drug Effects in Audiogenic Seizure-Susceptible Rats," Experimental Neurology, Academic Press Inc., 70:626-637 (1980)
  • Turkanis et al., "Electrophysiologic Properties of the Cannabinoids," J. Clin. Pharmacol., 21:449S-463S (1981)
  • Carlini et al., "Hypnotic and Antielpileptic Effects of Cannabidiol," J. Clin. Pharmacol., 21:417S-427S (1981)
  • Karler et al., "The Cannabinoids as Potential Antiepileptics," J. Clin. Pharmacol., 21:437S-448S (1981)
  • Consroe et al., "Antiepileptic Potential of Cannabidiol Analgos," J. Clin. Pharmacol., 21:428S-436S (1981)
  • Colasanti et al., "Ocular Hypotension, Ocular Toxicity,a nd Neurotoxicity in Response to Marihuana Extract and Cannabidiol," Gen Pharm., Pergamon Press Ltd., 15(6):479-484 (1984)
  • Colasanti et al., "Intraocular Pressure, Ocular Toxicity and Neurotoxicity after Administration of Cannabinol or Cannabigerol," Exp. Eye Res., Academic Press Inc., 39:251-259 (1984)
  • Volfe et al., "Cannabinoids Block Release of Serotonin from Platelets Induced by Plasma frm Migraine Patients," Int. J. Clin. Pharm. Res., Bioscience Ediprint Inc., 4:243-246 (1985)
  • Agurell et al., "Pharmacokinetics and Metabolism of Ɗ1 -Tetrahydrocannabinol and Other Cannabinoids with Emphasis on Man*," Pharmacological Reviews, 38(1):21-43 (1986)
  • Karler et al., "Different Cannabinoids Exhibit Different Pharmacological and Toxicological Properties,"NIDA Res. Monogr., 79:96-107 (1987)
  • Samara et al., "Pharmacokinetics of Cannabidiol in Dogs," Drug Metabolism and Disposition, 16(3):469-472 (1988)
  • Choi, "Glutamate Neurotoxicity and Diseases of the Nervous System," Neuron, Cell Press, 1:623-634 (1988)
  • Eshhar et al., "Neuroprotective and Antioxidant Activities of HU-211, A Novel NMDA Receptor Antagonist," European Journal of Pharmacology, 283:19-29 (1995)
  • Skaper et al., "The ALIAmide Palmitoylethanolamide and Cannabinoids, but not Anandamide, are Protective in a Delayed Postglutamate Paradigm of Excitotoxic Death in Cerebellar Granule Neurons," Neurobiology, Proc. Natl. Acad. Sci. USA, 93:3984-3989 (1996)
  • Alonso et al., "Simple Synthesis of 5-Substituted Resorcinols: A Revisited Family of Interesting Bioactive Molecules," J. Org. Chem., American Chemical Society, 62(2):417-421 (1997)
  • Combes et al. "A Simple Synthesis of the Natural 2,5-Dialkylresorcinol Free Radical Scavenger Antioxidant: Resorstation," Synthetic Communications, Marcel Dekker, Inc., 27(21):3769-3778 (1997)
  • Shohami et al., "Oxidative Stress in Closed-Head Injury: Brain Antioxidant Capacity as an Indicator of Functional Outcome," Journal of Cerebral Blood Flow and Metabolism, Lippincott-Raven Publishers, 17(10):1007-1019 (1997)
  • Zurier et al., "Dimethylheptyl-THC-11 OIC Acid," Arthritis & Rheumatism, 41(1):163-170 (1998)
  • Hampson et al., "Dual Effects of Anandamide on NMDA Receptor-Mediated Responses and Neurotransmission," Journal of Neurochemistry, Lippincott-Raven Publishers, 70(2):671-676 (1998)
  • Hampson et al., "Cannabidiol and (-)Ɗ9 -tetrahydrocannabiono are Neuroprotective Antioxidants," Medical Sciences, Proc. Natl. Acad. Sci. USA, 8268-8273 (1998)

Field of Search

 

Abstract

Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases.
The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia.
Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention. A particular disclosed class of cannabinoids useful as neuroprotective antioxidants is formula (I) wherein the R group is independently selected from the group consisting of H, CH3, and COCH3. ##STR1##

Other References

  • Windholz et al., The Merck Index, Tenth Edition (1983) p. 241, abstract No. 1723.
  • Mechoulam et al., "A Total Synthesis of d1-Ɗ1 -Tetrahydrocannabinol, the Active Constituent of Hashish1," Journal of the American Chemical Society, 87:14:3273-3275 (1965)
  • Mechoulam et al., "Chemical Basis of Hashish Activity," Science, 18:611-612 (1970)
  • Ottersen et al., "The Crystal and Molecular Structure of Cannabidiol," Acta Chem. Scand. B 31, 9:807-812 (1977)
  • Cunha et al., "Chronic Administration of Cannabidiol to Healthy Volunteers and Epileptic Patients1," Pharmacology, 21:175-185 (1980)
  • Consroe et al., "Acute and Chronic Antiepileptic Drug Effects in Audiogenic Seizure-Susceptible Rats," Experimental Neurology, Academic Press Inc., 70:626-637 (1980)
  • Turkanis et al., "Electrophysiologic Properties of the Cannabinoids," J. Clin. Pharmacol., 21:449S-463S (1981)
  • Carlini et al., "Hypnotic and Antielpileptic Effects of Cannabidiol," J. Clin. Pharmacol., 21:417S-427S (1981)
  • Karler et al., "The Cannabinoids as Potential Antiepileptics," J. Clin. Pharmacol., 21:437S-448S (1981)
  • Consroe et al., "Antiepileptic Potential of Cannabidiol Analgos," J. Clin. Pharmacol., 21:428S-436S (1981)
  • Colasanti et al., "Ocular Hypotension, Ocular Toxicity,a nd Neurotoxicity in Response to Marihuana Extract and Cannabidiol," Gen Pharm., Pergamon Press Ltd., 15(6):479-484 (1984)
  • Colasanti et al., "Intraocular Pressure, Ocular Toxicity and Neurotoxicity after Administration of Cannabinol or Cannabigerol," Exp. Eye Res., Academic Press Inc., 39:251-259 (1984)
  • Volfe et al., "Cannabinoids Block Release of Serotonin from Platelets Induced by Plasma frm Migraine Patients," Int. J. Clin. Pharm. Res., Bioscience Ediprint Inc., 4:243-246 (1985)
  • Agurell et al., "Pharmacokinetics and Metabolism of Ɗ1 -Tetrahydrocannabinol and Other Cannabinoids with Emphasis on Man*," Pharmacological Reviews, 38(1):21-43 (1986)
  • Karler et al., "Different Cannabinoids Exhibit Different Pharmacological and Toxicological Properties,"NIDA Res. Monogr., 79:96-107 (1987)
  • Samara et al., "Pharmacokinetics of Cannabidiol in Dogs," Drug Metabolism and Disposition, 16(3):469-472 (1988)
  • Choi, "Glutamate Neurotoxicity and Diseases of the Nervous System," Neuron, Cell Press, 1:623-634 (1988)
  • Eshhar et al., "Neuroprotective and Antioxidant Activities of HU-211, A Novel NMDA Receptor Antagonist," European Journal of Pharmacology, 283:19-29 (1995)
  • Skaper et al., "The ALIAmide Palmitoylethanolamide and Cannabinoids, but not Anandamide, are Protective in a Delayed Postglutamate Paradigm of Excitotoxic Death in Cerebellar Granule Neurons," Neurobiology, Proc. Natl. Acad. Sci. USA, 93:3984-3989 (1996)
  • Alonso et al., "Simple Synthesis of 5-Substituted Resorcinols: A Revisited Family of Interesting Bioactive Molecules," J. Org. Chem., American Chemical Society, 62(2):417-421 (1997)
  • Combes et al. "A Simple Synthesis of the Natural 2,5-Dialkylresorcinol Free Radical Scavenger Antioxidant: Resorstation," Synthetic Communications, Marcel Dekker, Inc., 27(21):3769-3778 (1997)
  • Shohami et al., "Oxidative Stress in Closed-Head Injury: Brain Antioxidant Capacity as an Indicator of Functional Outcome," Journal of Cerebral Blood Flow and Metabolism, Lippincott-Raven Publishers, 17(10):1007-1019 (1997)
  • Zurier et al., "Dimethylheptyl-THC-11 OIC Acid," Arthritis & Rheumatism, 41(1):163-170 (1998)
  • Hampson et al., "Dual Effects of Anandamide on NMDA Receptor-Mediated Responses and Neurotransmission," Journal of Neurochemistry, Lippincott-Raven Publishers, 70(2):671-676 (1998)
  • Hampson et al., "Cannabidiol and (-)Ɗ9 -tetrahydrocannabiono are Neuroprotective Antioxidants," Medical Sciences, Proc. Natl. Acad. Sci. USA, 8268-8273 (1998)
 
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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
MedicationDelta-9-THC

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.

 

OBJECTIVES

All Conditions Benefited by
Medical Marijuana

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Route(s)Oral
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
Full text

Marijuana Use Does Not Accelerate HIV Infection

 

ISLAMABAD: Short-term cannabis use does not seem to adversely affect CD4+ cell counts or viral loads in HIV -infected patients, according to a report published in the August 19th issue of the Annals of Internal Medicine.

In HIV-infected patients, marijuana has been used as an appetite stimulant and as a treatment for the nausea associated with some antiretroviral agents. However, concern has been raised that such therapy could have a harmful effect on disease status, because in theory, cannabinoid use could increase HIV levels by impairing the immune response or by interfering with the activity of protease inhibitors.

Previously it was shown that short-term marijuana use did not influence nelfinavir metabolism. Although marijuana use did produce a drop in indinavir levels, this fall was small and unlikely to be clinically meaningful. However, it still remained unclear whether cannabinoid use had an effect on viral load or CD+ cell counts.

To investigate, Dr. Donald I. Abrams, from the University of California at San Francisco, and colleagues assessed the outcomes of 67 HIV-infected patients who were randomly assigned to use marijuana cigarettes, cannabinoid capsules, or sugar pills (placebo) three times daily for 21 days. All of the patients had been receiving the same antiretroviral regimen, which included indinavir or nelfinavir, for at least 8 weeks before the study began.

More than half of the subjects in each group had undetectable viral loads throughout the study, the researchers note. Although not statistically significant, marijuana and cannabinoid use were actually associated with a slight drop in viral load compared with placebo use.

Marijuana and cannabinoid use did not produce a drop in CD4+ or CD8+ cell counts. In fact, compared with placebo use, treatment with these agents was actually associated with a slight increase in cell counts.

The results suggest that short-term cannabinoid use is not unsafe for patients with HIV infection, the authors note. "Further studies investigating the therapeutic potential of marijuana and other cannabinoids in patients with HIV infection and other populations are ongoing and should provide additional safety information over longer exposure periods," they write.

Thanks Pakistan News Servises Tribune

 

 

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Recent clinical experience with dronabino

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
MedicationDelta-9-THC

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.

 

 

OBJECTIVES

All Conditions Benefited by
Medical Marijuana


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Route(s)Oral
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.
Full text 

Denbinobin... inhibits HIV-1 replication through an NF-kappaB-dependent pathway

Sánchez-Duffhues G, Calzado MA, de Vinuesa AG, Caballero FJ, Ech-Chahad A, Appendino G, Krohn K, Fiebich BL, Muñoz E

Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Facultad de Medicina, Córdoba, Spain.

Anthraquinones and structurally related compounds have been recently shown to exert antiviral activities and thus exhibit a therapeutic potential. In this study we report the isolation of the 1,4-phenanthrenequinone, denbinobin, from a variety of Cannabis sativa. Denbinobin does not affect the reverse transcription and integration steps of the viral cycle but prevents HIV-1 reactivation in Jurkat T cells activated by TNFalpha, mAbs anti-CD3/CD28 or PMA.

In addition, denbinobin inhibits HIV-1-LTR activity at the level of transcription elongation and also TNFalpha-induced HIV-1-LTR transcriptional activity. We found that denbinobin prevents the binding of NF-kappaB to DNA and the phosphorylation and degradation of NF-kappaB inhibitory protein, IkappaBalpha, and inhibits the phosphorylation of the NF-kappaB p65 subunit in TNFalpha-stimulated cells.

These results highlight the potential of the NF-kappaB transcription factor as a target for natural anti-HIV-1 compounds such as 1,4-phenanthrenequinones, which could serve as lead compounds for the development of an alternative therapeutic approach against AIDS.

Published 28 October 2008 in Biochem Pharmacol, 76(10): 1240-50.
Full-text of this article is available online (may require subscription).

 

 

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