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INTERACTIONS WITH OTHER DRUGS & Cannabis studies completed

Overview

Some people use marijuana for recreational purposes, to create a sense of well being or to alter the senses. It is either taken by mouth or smoked (inhaled).


Marijuana is also taken by mouth for medicinal purposes. A cannabinoid from marijuana, tetrahydrocannabinol (THC), is used in the prescription-only, FDA-approved product dronabinol (Marinol) for the treatment of weight loss or appetite loss due to AIDS and for nausea and vomiting caused by cancer chemotherapy.


Cannabinoids are at least as effective as some conventional medications for nausea, including prochlorperazine (Compazine), metoclopramide (Reglan), chlorpromazine (Compazine), and thiethylperazine (Torecan).

Cannabinoids from marijuana also appear to be similar to codeine for treatment of pain. However, extreme sleepiness and other central nervous system effects make cannabinoids undesirable as painkillers.

Other cannabinoids from marijuana have also been used by mouth to treat symptoms of multiple sclerosis (MS).

Some people inhale cannabis for medicinal purposes. Cannabis is smoked for nausea, glaucoma, appetite stimulation, mucous membrane inflammation, leprosy, fever, dandruff, hemorrhoids, obesity, asthma, urinary tract infections, cough, anorexia associated with weight loss in AIDS patients, pain, and multiple sclerosis. It is also inhaled to weaken the immune system after kidney transplant to lessen the chance of transplant rejection.

Avoid confusion with hemp, a distinct variety of Cannabis sativa cultivated for its fiber and seeds, which contains less than 1% THC.


How does it work? Marijuana contains chemicals that work by binding to specific sites in the brain and on the nerves.

Science and Research

2012 - Study ~ Synergistic interaction of pregabalin with the synthetic cannabinoid WIN 55,212-2 mesylate in the hot-plate test in mice: an isobolographic analysis.

2012 - Study ~ Synergistic interaction of pregabalin with the synthetic cannabinoid WIN 55,212-2 mesylate in the hot-plate test in mice: an isobolographic analysis.

2012 - Study ~ Changes of Blood Endocannabinoids during Anaesthesia: a Special Case for Fatty Acid Amide Hydrolase Inhibition by Propofol?

2012 - Study ~ Effects of amphetamine on dopamine release in the rat nucleus accumbens shell region depend on cannabinoid CB1 receptor activation.

2012 - Study ~ Effect of ACEA-a selective cannabinoid CB1 receptor agonist on the protective action of different antiepileptic drugs in the mouse pentylenetetrazole-induced seizure model.

2011 - Study ~ Cannabidiol Attenuates Cisplatin-Induced Nephrotoxicity by Decreasing Oxidative/Nitrosative Stress, Inflammation, and Cell Death

2011 - Study ~ Cannabidiol Attenuates Cisplatin-Induced Nephrotoxicity by Decreasing Oxidative/Nitrosative Stress, Inflammation, and Cell Death

2011 - Study ~ Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol)

2011 - Study ~ Combined effects of acute, very-low-dose ethanol and delta(9)-tetrahydrocannabinol in healthy human volunteers

2011 - Study ~ Inhibition of monoacylglycerol lipase (MAGL) attenuates NSAID-induced gastric hemorrhages in mice.

2011 - Study ~ Cannabinoid system and cyclooxygenases inhibitors

2011 - Study ~ Possible involvement of the endocannabinoid system in memory modulation effect of general anesthetics

2011 - Study ~ Role of GLT-1 transporter activation in prevention of cannabinoid tolerance by the beta-lactam antibiotic, ceftriaxone, in mice.

2011 - Study ~ Cannabis in Palliative Medicine: Improving Care and Reducing Opioid-Related Morbidity

2011 - Study ~ Cannabinoid-opioid interaction in chronic pain.

2011 - Study ~ A combined preclinical therapy of cannabinoids and temozolomide against glioma.

2011 - Study ~ The safety of modafinil in combination with oral Δ9-tetrahydrocannabinol in humans.

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

2011 - Study ~ The G protein-coupled cannabinoid-1 (CB(1)) receptor of mammalian brain: Inhibition by phthalate esters in vitro.

2011 - Study ~ The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects.

2011 - Study ~ Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats

2011 - Study ~ Combined effects of THC and caffeine on working memory in rats.

2011 - Study ~ Pretreatment with Δ9-tetrahydrocannabinol (THC) increases cocaine-stimulated activity in adolescent but not adult male rats

2011 - Study ~ Previous exposure to delta9-tetrahydrocannibinol enhances locomotor responding to but not self-administration of amphetamine.

2011 - Study ~ THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats.

2011 - Study ~ Pharmacokinetics of a combination of Δ9-tetrahydro-cannabinol and celecoxib in a porcine model of hemorrhagic shock.

2011 - Study ~ Low-volume binary drug therapy for the treatment of hypovolemia.

2011 - Study ~ Efavirenz interference in urine screening immunoassays for tetrahydrocannabinol.

2011 - Study ~ Clozapine and SCH 23390 prevent the spatial working memory disruption induced by Δ9-THC administration into the medial prefrontal cortex.

2011 - News ~ Pharmaceutical Drug-Herb Interaction List

2011 - News ~ What Causes False Positives in Marijuana Drug Testing?

2010 - Study ~ THC Prevents MDMA Neurotoxicity in Mice.

2010 - Study ~ Attenuation of morphine antinociceptive tolerance by a CB(1) receptor agonist and an NMDA receptor antagonist: Interactive effects.

2010 - Study ~ Influence of ethanol on cannabinoid pharmacokinetic parameters in chronic users

2010 - Study ~ Methamphetamine neurotoxicity increases brain expression and alters behavioral functions of CB₁ cannabinoid receptors.

2010 - Study ~ The safety of modafinil in combination with oral Δ9-tetrahydrocannabinol in humans

2010 - Study ~ Opioid antagonism enhances marijuana's effects in heavy marijuana smokers.

2010 - Study ~ The analgesic potential of cannabinoids.

2010 - Study - Probable Interaction Between Warfarin and Marijuana Smoking

2010 - Study - Adolescent cannabis use increases risk for cocaine-induced paranoia

2010 - News ~ Chocolate: The Good, the Bad and the Angry

2010 - News ~ Cocoa and the Search for Dietary Cannabinoids

2010 - News ~ Cannabis-enhancing plant to be marketed worldwide as new drug

2010 - News ~ Acetaminophen Synergizes Through the CB1 Receptor

2009 - Study ~ Effects of Cannabinoids on Caffeine Contractures in Slow and Fast Skeletal Muscle Fibers of the Frog

2009 - Study ~ Cannabinoid receptor-independent cytotoxic effects of cannabinoids in human colorectal carcinoma cells: synergism with 5-fluorouracil.

2009 - Study ~ Pharmacological synergism between cannabinoids and paclitaxel in gastric cancer cell lines.

2009 - Study ~ Delayed onset of seizures and toxicity associated with recreational use of Bromo-dragonFLY.

2009 - Study ~ An unusual cause of syncope

2009 - Study - Cannabis Coadministration Potentiates the Effects of "Ecstasy" on Heart Rate and Temperature in Humans

2009 - Study - Induction dose of propofol in patients using cannabis

2009 - Study - Interaction of the cannabinoid and opioid systems in the modulation of nociception

2009 - Study - Cannabis coadministration potentiates the effects of "ecstasy" on heart rate and temperature in human

2009 - Study - Cannabinoids, Opioids and MDMA: Neuropsychological Interactions Related to Addiction

2009 - News - Smoking Pot, Cigarettes Ups COPD Risk
2009 - Study ~ Enhancing the in vitro cytotoxic activity of Δ9-tetrahydrocannabinol in leukemic cells through a combinatorial approach

2008 - Study - Enhancing the in vitro cytotoxic activity of Δ9-tetrahydrocannabinol in leukemic cells through a combinatorial approach

2008 - Study ~ Repeated Cannabinoid Injections into the Rat Periaqueductal Gray Enhances Subsequent Morphine Antinociception

2008 - Study ~ Priapism, ecstasy, and marijuana: is there a connection?

2008 - Study ~ Propofol Sedation Is Reduced by {Delta}9-Tetrahydrocannabinol in Mice

2008 - Study ~ Additive Interaction of the Cannabinoid Receptor I Agonist Arachidonyl-2-chloroethylamide with Etomidate in a Sedation Model in Mice

2008 - Study ~ Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1).

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

2007 - Study - Synergy between Delta(9)-tetrahydrocannabinol and morphine in the arthritic rat

2007 - Study ~ Opioid Antagonism of Cannabinoid Effects: Differences between Marijuana Smokers and Nonmarijuana Smokers

2007 - Study ~ Low dose combination of morphine and Δ9-tetrahydrocannabinol circumvents antinociceptive tolerance and apparent desensitization of receptors

2007 - Study - Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel

2007 - Study ~ Antinociceptive Synergy Between the Cannabinoid Receptor Agonist WIN 55,212-2 and Bupivacaine in the Rat Formalin Test

2007 - Study - The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids

2007 - Study ~ Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats.

2007 - Study ~ Additive Effects of Timolol and Cannabinoids on Intraocular Pressure in a Rat Glaucoma Model

2007 - Study ~ Propranolol effects on acute marihuana intoxication in man

2007 - News - Cannabinoids, in combination with (NSAIDS), produce a synergistic analgesic effect

2007 - News ~ Science: The use of cannabis does not influence the efficacy of two anti-cancer drugs, a clinical study finds

2006 - Study ~ Modulation of paraoxon toxicity by the cannabinoid receptor agonist WIN 55,212-2.

2006 - Study ~ Local interactions between anandamide, an endocannabinoid, and ibuprofen, a nonsteroidal anti-inflammatory drug, in acute and inflammatory pain

2006 - Study ~ Benefits of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain - a randomized controlled trial.

2006 - Study ~ Arachidonyl-2'-chloroethylamide, a highly selective cannabinoid CB1 receptor agonist, enhances the anticonvulsant action of valproate in the mouse maximal electroshock-induced seizure model.

2006 - Study - Synergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine

2006 - Study - Add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain

2006 - News ~ Cannabinoids Enhance Analgesic Effects Of Anti-Inflammatory Drugs, Study Says

2004 - Study - Cyclic Antidepressants

2004 - Study ~ Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA ("Ecstasy") in rats.

2004 - Study ~ Cannabis Abuse is Not a Risk Factor for Treatment Outcome in Methadone Maintenance Treatment: a 1-year Prospective Study in an Israeli Clinic.

2003 - Study - Cannabis reduces opioid dose in the treatment of chronic non-cancer pain

2003 - Study ~ Haloperidol, but not clozapine, produces dramatic catalepsy in delta9-THC-treated rats: possible clinical implications.

2003 - Study ~ Manipulation of the endocannabinoid system by a general anaesthetic.

2003 - Study ~ Modulation of oral morphine antinociceptive tolerance and naloxone-precipitated withdrawal signs by oral Delta 9-tetrahydrocannabinol.

2003 - Study ~ Topical cannabinoid enhances topical morphine antinociception.

2002 - Study ~ Decrease in efficacy and potency of nonsteroidal anti-inflammatory drugs by chronic delta(9)-tetrahydrocannabinol administration.

2002 - Study ~ Tobacco and Cannabis Smoking Cessation Can Lead to Intoxication with Clozapine or Olanzapine.

2001 - Study ~ Protective effects of cannabinoid receptor ligands analogous to anandamide against cocaine toxicity.
2000 - Study ~ Involvement of central and peripheral cannabinoid receptors in the regulation of heart resistance to arrhythmogenic effects of epinephrine.
1999 - Study ~ Case report: adverse effects of taking tricyclic antidepressants and smoking marijuana.
1996 - Study ~ Marijuana and chocolate.
1995 - Study ~ Anandamide and delta 9-THC dilation of cerebral arterioles is blocked by indomethacin

1994 - Study ~ Marihuana smoking increases plasma cocaine levels and subjective reports of euphoria in male volunteers.

1992 - Study ~ Marihuana attenuates the rise in plasma ethanol levels in human subjects.

1991 - Study - Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting.

1991 - Study ~ Flashback Following Use of Cannabis--a Review

1987 - Study ~ Respiratory effects of cocaine "freebasing" among habitual users of marijuana with or without tobacco

1983 - Study ~ Adverse Interaction Between Disulfiram and Marijuana: a Case Report.

1983 - Study ~ ANALGESIC INTERACTION BETWEEN NITROUS OXIDE AND DELTA-9-TETRAHYDEROCANNABINOL IN THE RAT

1983 - Study ~ Adverse Interaction Between Disulfiram and Marijuana: a Case Report.

1983 - Study ~ ANALGESIC INTERACTION BETWEEN NITROUS OXIDE AND DELTA-9-TETRAHYDEROCANNABINOL IN THE RAT

1981 - Study ~ Tetrahydrocannabinol potentiates reserpine-induced hypokinesia.

1980 - Study ~ Effects of drugs on behavior in pigeons tolerant to delta 9-tetrahydrocannabinol.
1978 - Study ~ Enhanced Biotransformation of Theophylline in Marihuana and Tobacco Smokers.

1977 - Study ~ Cannabidiol --antiepileptic drug comparisons and interactions in experimentally induced seizures in rats.

1977 - Study ~ The effect of delta 9-tetrahydrocannabinol, cannabidiol, and cannabinol on the anaesthesia induced by various anaesthetic agents in mice.

1977 - Study ~ Propranolol Effects on Acute Marihuana Intoxication in Man.

1976 - Study ~ The Effects of Delta-9-Tetrahydrocannabinol (Cannabis) on Cardiac Performance with and without Beta Blockade

1975 - Study - The analgesic properties of delta-9-tetrahydrocannabinol and codeine

1975 - Study ~ Combination of delta9-tetrahydrocannabinol with oxymorphone or pentobarbital: Effects on ventilatory control and cardiovascular dynamics.

1975 - Study ~ Interactions in man of delta-9-tetrahydrocannabinol. II. Cannabinol and cannabidiol.

1975 - Study ~ Effects of marihuana combined with secobarbital.

1974 - Study - Interaction of cannabis and general anaesthetic agents in mice
1973 - Study ~ Cardiovascular and respiratory effects of cannabis extracts and 1-tetra-hydrocannabinol
( 1-THC).

1972 - Study -  Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism

1972 - Study ~ Proceedings: Effects of chronic and acute cannabis treatment upon thiopentone anaesthesia in rabbits.

1970 - Study ~ INTERACTIONS OF Δ1-TETRAHYDROCANNABINOL WITH BARBITURATES AND METHAMPHETAMINE



Cyclic Antidepressants

 On October 15, 2004, the FDA has concluded that antidepressant medications increase the risk of suicidal thinking and behavior in children and adolescents with depression and other psychiatric disorders. If you have questions or concerns, discuss them with your health care provider

 

"What I remember most about being depressed was always being exhausted. I could never get to sleep at night, and when I did, I had nightmares. Then I'd wake up in the morning and have to drag myself to work. And in all that time—four or five years, I guess—I never once enjoyed anything. I was actually planning my own suicide when my doctor referred me to a psychiatrist who put me on imipramine. For the first time in years, I finally began to get some pleasure out of life."

—Sam, 43

Before the SSRIs, tricyclics were the first line of defense against encroaching depression, and had been ever since imipramine's release in 1958 under the brand name Tofranil.

Today, tricyclics are a less popular choice than the new generation of antidepressants, but they're still an important weapon in the antidepressant arsenal for a subset of people who don't respond to anything else.

Before tricyclics were developed, psychiatrists treating severely depressed clients had only two real choices: amphetamines or electroshock therapy.

Imipramine was discovered by Swiss scientists searching for a successful schizophrenia treatment; it turned out that imipramine didn't do much for schizophrenia at all. What it did do very well was perk up depressed patients.

 

Common Cyclic Antidepressants

Lower doses are used with elderly patients)

Drug Usual Effective Daily Dose
Amitriptyline
(Elavil, Endep, Emitrip, Enovil)
150–300 mg
Amoxapine
(Asendin)
150–400 mg
Clomipramine
(Anafranil)
100–150 mg
Desipramine
(Norpramin, Pertofrane)
100–300 mg
Doxepin
(Adapin, Sinequan)
75–300 mg
Imipramine
(Janimine, Tipramine, Tofranil, Tofranil-PM)
150–300 mg
Maprotiline
(Ludiomil)
75–150 mg
Nortriptyline
(Pamelor, Aventyl)
50–150 mg
Protriptyline
(Vivactil)
15–60 mg
Trimipramine
(Surmontil)

75–150 mg

With the discovery of imipramine, doctors finally had a drug that relieved a person's underlying depression.

When scientists realized how effective imipramine was—about 70 percent of depressed patients responded to this drug—they flocked to the laboratories in search of similar drugs based on imipramine's three-ring ("tricyclic") antihistaminic chemical structure.

Before long, laboratories all over the country began churning out tricyclic clones, each one a little different from, but none any better than, imipramine itself.

A later-developed drug in this class, maprotiline (Ludiomil), had four rings and was therefore called "tetracyclic." Taken together, the tricyclics and tetracyclics are known as "heterocyclics" or "cyclics."

But while all these cyclics were effective, not one provided the perfect solution to depression for which scientists had been searching.


 

Dronabinol and prochlorperazine in combination

TitleDronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting.
Author(s)Lane M, Vogel CL, Ferguson J, Krasnow S, Saiers JL, Hamm J
Journal, Volume, IssueJournal of Pain and Symptom Management 1991;6:352-359
Major outcome(s)prochlorperazine better than THC, both drugs combined better than both alone
 
IndicationNausea/vomiting;Cancer;Cancer chemotherapyAbstract
MedicationDelta-9-THC

Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group, multicenter study.

Patients were randomized to receive either 1) dronabinol 10 mg every 6 hr plus placebo; 2) placebo plus prochlorperazine 10 mg every 6 hr; or 3) dronabinol and prochlorperazine, each 10 mg every 6 hr.

Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy; all was given orally.

Only 29% of patients in group 3 versus 47% in group 1 and 60% in group 2 experienced nausea after chemotherapy.

In addition, the median duration per episode and severity of nausea were significantly less with combination therapy.

Vomiting occurred after chemotherapy in 41%, 55%, and 35% of patients in groups 1, 2, and 3, respectively.

The median duration per episode of vomiting was 1 min in group 3 versus two in group 1 and four in group 2.

Side effects, primarily CNS, were more common in group 1 than in group 2; addition of prochlorperazine to dronabinol appeared to decrease the frequency of dysphoric effects seen with the latter agent.

The combination was significantly more effective than was either single agent in controlling chemotherapy-induced nausea and vomiting.

 

 
Route(s)Oral
Dose(s) 
Duration (days)10 mg every 6 hr
Participants67 patients on various cancer chemotherapie
DesignControlled study
Type of publication 
Address of author(s) 
Full text

Cannabinoids, in combination with (NSAIDS), produce a synergistic analgesic effect

 Ankara, Turkey: Cannabinoids, when administered in combination with non-steroidal anti-inflammatory drugs (NSAIDS), produce a synergistic analgesic effect, according to preclinical data published in the February issue of the journal Anesthesia & Analgesia.

A research team at the Trakya University in Turkey investigated the analgesic interaction between cannabinoids and NSAIDS in mice. "Analysis showed additive interactions between [cannabinoids] and [NSAIDS] when they were co-administered systematically in an inflammatory visceral pain model," investigators concluded. "The combination of cannabinoids and NSAIDS may have utility in the pharmacotherapy of pain."

http://www.norml.org/index.cfm?Group_ID=6819

 

 
 
 
 
 

Add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain

Title[Benefits of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain - a randomized controlled trial.] [Article in German]
Author(s)Pinsger M, Schimetta W, Volc D, Hiermann E, Riederer F, Polz W.
Journal, Volume, IssueWien Klin Wochenschr. 2006 Jun;118(11-12):327-35.
Major outcome(s)Nabilone caused a significant reduction in pain and improvement of quality of life.
 
IndicationPainAbstract
MedicationNabilone

OBJECTIVE: The aim of this study was to investigate the efficacy and efficiency of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain.

Of major interest were the evaluation of the influence the treatment had on pain and on quality of life as well as the subjective assessment of positive effects and side effects by the study participants.

METHODS: The placebo-controlled double-blinded pilot study was divided into a 14 week cross-over period (two 4 week medication phases plus wash-out phases) followed by a 16 week medication switch period with free choice of the study drugs (drug A and drug B) by the study participants.

The principal inclusion criterion was chronic therapy-resistant pain in causal relationship with a pathologic status of the skeletal and locomotor system.

The study participants chose the dosage of the study drug themselves (between 1 und 4 capsules/day, in the case of nabilone this corresponds to (1/4)-1 mg/day).

Pain intensity was assessed by a visual analogue scale (VAS), quality of life by the Mezzich & Cohen QOL-score. RESULTS: Altogether, 30 patients were included and analyzed.

From the results, it is obvious that throughout the cross-over periods the nabilone treatment was superior (medians [25%-; 75%-percentiles]: nabilone/placebo): decrease of the average spinal pain intensity within the last 4 weeks (DeltaVAS) 0.9 [0.0; 2.0] / 0.5 [0.0; 1.7], decrease of the current spinal pain intensity (DeltaVAS) 0.6 [0.0; 2.5] / 0.0 [-1.0, 1.0] (p = .006), decrease of the average headache intensity within the last 4 weeks (DeltaVAS) 1.0 [-1.0; 2.4] / 0.2 [-0.9; 1.0], increase of the number of days without headache within the last 4 weeks 2.0 [0.0; 6.5] / 0.0 [-5.0; 4.0], increase of the quality of life (DeltaQOL-Score) 5.0 [0.8; 10.8] / 2.0 [-2.3; 8.0].

In the medication switch period, the number of study participants who favoured nabilone (nabilone intake >/=85% of all medication days) was more than 4 times higher than those who favoured placebo.

The number of days with nabilone intake was clearly higher than the number with placebo intake (medians: 89% vs. 11% of all medication days, p = .003).

CONCLUSION: In summary, the study results allow the conclusion that a majority of patients with chronic pain classify nabilone intake in addition to the standard treatment as a measure with a positive individual benefit-riskratio.

Thus, this kind of treatment may be an interesting and attractive enrichment of analgetic therapy concepts.

 
 
 
 
 
Route(s)Oral
Dose(s)0,25-1mg
Duration (days)210
Participants30 patients with chronic pain
DesignControlled study
Type of publicationMedical journal
Address of author(s)Confraternitat, Privatklinik Josefstadt, Wien, Austria, m.pinsger@nextra.at.
Full text

Synergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine

TitleSynergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine.
Author(s)Roberts JD, Gennings C, Shih M.
Journal, Volume, IssueEur J Pharmacol 2006;530(1-2):54-8.
Major outcome(s)There was a synergistic effect between THC and morphine on the affective component of pain but not on the sensory component
 
IndicationPainAbstract
MedicationDelta-9-THC

Evidence for an analgesic interaction between delta-9-tetrahydrocannabinol (Delta(9)-THC) and morphine was sought using an experimental pain model applied to normal volunteers.

The study incorporated a double blinded, four treatment, four period, four sequence, crossover design.

Subjects received Delta(9)-THC 5 mg orally or placebo and 90 min later morphine 0.02 mg/kg intravenously or placebo.

Fifteen minutes later subjects rated the pain associated with the application of thermal stimuli to skin using two visual analog scales, one for the sensory and one for the affective aspects of pain.

Among sensory responses, neither morphine nor Delta(9)-THC had a significant effect at the doses used, and there was no significant interaction between the two.

Among affective responses, although neither morphine nor Delta(9)-THC had a significant effect, there was a positive analgesic interaction between the two (p=0.012), indicating that the combination had a synergistic affective analgesic effect.

The surprisingly limited reported experimental experience in humans does not support a role for Delta(9)-THC as an analgesic or as an adjunct to cannabinoid analgesia, except for our finding of synergy limited to the affective component of pain.

Comparison of our results with those of others suggests that extrapolation from experimental pain models to the clinic is not likely to be a straight-forward process.

Future studies of Delta(9)-THC or other cannabinoids in combination with opiates should focus upon clinical rather than experimental pain.

 
 
Route(s)Oral
Dose(s)5 mg
Duration (days)1
ParticipantsHealthy subjects
DesignControlled study
Type of publicationMedical journal
Address of author(s)Massey Cancer Center and the Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Full text 

The analgesic properties of delta-9-tetrahydrocannabinol and codeine

TitleThe analgesic properties of delta-9-tetrahydrocannabinol and codeine.
Author(s)Noyes R Jr, Brunk SF, Avery DAH, Canter AC
Journal, Volume, IssueClinical Pharmacology and Therapeutics 1975;18(1):84-89
Major outcome(s)milde analgesic effect; with 20 mg THC strong adverse effects
 
IndicationCancer; PainAbstract
MedicationDelta-9-THC

The administration of single oral doses of delta-9- tetrahydrocannabinol (THC) to patients with cancer pain demonstrated a mild analgesic effect.

At a dose of 20 mg, however, THC induced side effects that would prohibit its therapeutic use including somnolence, dizziness, ataxia, and blurred vision.

Alarming adverse reactions were also observed at this dose. THC, 10 mg, was well tolerated and, despite its sedative effect, may analgesic potential.


 
 
 
 
 
 
Route(s)Oral
Dose(s)10-20 mg
Duration (days) 
Participants36 cancer patients
DesignControlled study
Type of publication 
Address of author(s) 
Full text 

Synergy between Delta(9)-tetrahydrocannabinol and morphine in the arthritic rat

Cox ML, Haller VL, Welch SP

Eur J Pharmacol 2007 Apr 20.

We have shown in past isobolographic studies that a small amount of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) can enhance morphine antinociception in mice. However, previous studies of the Delta(9)-THC/morphine interaction were performed using normal mice or rats and evaluated acute thermal antinociception.

Less is known about cannabinoid and opioid interactions involved in mechanical nociception and in chronic inflammatory pain models, such as Freund's complete adjuvant-induced arthritic model. One fixed-ratio combination was chosen for testing the interaction between Delta(9)-THC and morphine in the Freund's adjuvant-induced arthritic model.

This combination represented a 1:1 ratio of the drugs and thus consisted of equieffective doses ranging from 0.1 to 5 mg/kg Delta(9)-THC and from 0.1 to 5 mg/kg morphine. The combination ED(50) value for the fixed ratios (total dose) in relation to the ED(50) value of the drugs alone was determined.

The isobolographic analysis indicated a synergistic interaction between Delta(9)-THC and morphine in both the non-arthritic and the arthritic rats.

Since Freund's adjuvant-induced alteration in endogenous opioid tone has been previously shown, our data indicate that such changes did not preclude the use of Delta(9)-THC and morphine in combination. As with acute preclinical pain models in which the Delta(9)-THC/morphine combination results in less tolerance development, the implication of the study for chronic pain conditions is discussed.

 


 

Cannabis reduces opioid dose in the treatment of chronic non-cancer pain

TitleCannabis reduces opioid dose in the treatment of chronic non-cancer pain.
Author(s)Lynch ME, Clark AJ.
Journal, Volume, IssueJ Pain Symptom Manage. 2003 Jun;25(6):496-8.
Major outcome(s)Improvement in pain, spasticity, bladder spasm, and sleep.
 
IndicationPainAbstract
MedicationCannabis

 

No abstract available.
First of three case reports:
A 47-year-old woman with a ten-year history of chronic progressive multiple sclerosis (MS) head headache, multisite joint pain, bladder spasm, and leg spasticity.

Ambulation was significantly compromised by the joint pain and leg spasticity.

She was wheelchair dependent, and also suffered from severe insomnia and fatigue, which she attributed to the combination of pain, bladder spasm, and leg spasticity.

Physical examination revealed paraparesis, weakness in the left upper extremity, tremor involving both hands, intranuclear ophthalmoplegia and l’Hermitte’s sign.

Previous treatment included steroids, physiotherapy, acupuncture, interdisciplinary pain management, intramuscular injections of botulinum toxin, amitritryptiline, fluoxetine, amantadine, acetaminophen with codeine, oxycodone, nonsteroidal anti-inflammatory drugs (NSAIDS), and baclofen.

The patients’ medications prior to access to smoked marijuana consisted of long-acting morphine 75 mg per day, tizanidine 24 mg per day, and sertraline 150 mg at bedtime.

In spite of these treatments, the patient did not obtain adequate control of her pain, spasticity, or sleep.


The patient received permission for access to smoked marijuana and began to use a dose of 2-4 puffs of smoked marijuana at bedtime on a regular basis.

Over the next six months, the morphine was reduced to 45 mg per day, tizanidine to 6 mg once per day, and setraline to between 100 mg and 150 mg at bedtime.

The patient reported improvement in pain, spasticity, bladder spasm, and sleep.

The patient denied any adverse side effects, other than she felt somewhat “high” if she smoked more than 4 puffs per dose.

She was able to adjust the dose so that this did not occur.

The patient received legal access in the autumn of 2000 and continues to use marijuana.


 
 
 
 
 

 

Route(s)Inhalation
Dose(s) 
Duration (days) 

 
DesignUncontrolled case report
Type of publicationMedical journal
Address of author(s)Queen Elizabeth II Health Sciences Center, Dalhousie University, Halifax, Nova Scotia, Canada
Full text 

Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel

TitleMedicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel.
Author(s)Engels FK, de Jong FA, Sparreboom A, Mathot RA, Loos WJ, Kitzen JJ, de Bruijn P, Verweij J, Mathijssen RH.
Journal, Volume, IssueOncologist 2007;12(3):291-300.
Major outcome(s)Cannabis did not influence the pharmacokinetics of the two anti-cancer drugs
 
IndicationCancer;Cancer chemotherapyAbstract
MedicationCannabis

OBJECTIVE: To date, data regarding the potential of cannabinoids to modulate cytochrome P450 isozyme 3A (CYP3A) activity are contradictory.

Recently, a standardized medicinal cannabis product was introduced in The Netherlands.

We anticipated an increased use of medicinal cannabis concurrent with anticancer drugs, and undertook a drug-INTERACTION study to evaluate the effect of concomitant medicinal cannabis on the pharmacokinetics of irinotecan and docetaxel, both subject to CYP3A-mediated biotransformation.

PATIENTS AND METHODS: Twenty-four cancer patients were treated with i.v. irinotecan (600 mg, n = 12) or docetaxel (180 mg, n = 12), followed 3 weeks later by the same drugs concomitant with medicinal cannabis (200 ml herbal tea, 1 g/l) for 15 consecutive days, starting 12 days before the second treatment.

Blood samples were obtained up to 55 hours after dosing and analyzed for irinotecan and its metabolites (SN-38, SN-38G), respectively, or docetaxel.

Pharmacokinetic analyses were performed during both treatments. Results are reported as the mean ratio (95% confidence interval [CI]) of the observed pharmacokinetic parameters with and without concomitant medicinal cannabis.

RESULTS: Medicinal cannabis administration did not significantly influence exposure to and clearance of irinotecan (1.04; CI, 0.96-1.11 and 0.97; CI, 0.90-1.05, respectively) or docetaxel (1.11; CI, 0.94-1.28 and 0.95; CI, 0.82-1.08, respectively).

CONCLUSION: Coadministration of medicinal cannabis, as herbal tea, in cancer patients treated with irinotecan or docetaxel does not significantly influence the plasma pharmacokinetics of these drugs.

The evaluated variety of medicinal cannabis can be administered concomitantly with both anticancer agents without dose adjustments.


 
 
Route(s)Oral
Dose(s)200 ml cannabis tea
Duration (days)15
Participants24 cancer patients treated with irinotecan or docetaxel
DesignOpen study
Type of publicationMedical journal
Address of author(s)Department of Medical Oncology, Erasmus MC University Medical Center Rotterdam - Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Full text

Interaction of cannabis and general anaesthetic agents in mice

Br J Pharmacol. 1974 April; 50(4): 593–599.
PMCID: PMC1776719
 

Cannabis Coadministration Potentiates the Effects of "Ecstasy" on Heart Rate and Temperature in Humans

Dumont G, Kramers C, Sweep F, Touw D, van Hasselt J, de Kam M, van Gerven J, Buitelaar J, Verkes R 

Clin Pharmacol Ther 2009 May 13.

This study assessed the acute physiologic effects over time of (co)administration of Delta9-tetrahydrocannabinol (Delta9-THC) (the main psychoactive compound of cannabis) and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") in 16 healthy volunteers.

Pharmacokinetics and cardiovascular, temperature, and catecholamine responses were assessed over time.

Both single-drug conditions robustly increased heart rate, and coadministration showed additive effects.

MDMA increased epinephrine and norepinephrine concentrations, whereas THC did not affect the catecholamine response.

Coadministration of MDMA and THC attenuated the increase of norepinephrine concentrations relative to administration of MDMA alone.

These results show that THC mediates heart rate increase independent of sympathetic (catecholaminergic) activity, probably through direct cannabinoid receptor type 1 (CB(1)) agonism in cardiac tissue. Furthermore, THC coadministration did not prevent MDMA-induced temperature increase, but it delayed the onset and prolonged the duration of temperature elevation.

These effects may be of particular relevance for the cardiovascular safety of ecstasy users who participate in energetic dancing in nightclubs with high ambient temperature.Clinical Pharmacology & Therapeutics (2009); advance online publication 13 May 2009. doi:10.1038/clpt.2009.62.

 

 

 


 

Enhancing the in vitro cytotoxic activity of Δ9-tetrahydrocannabinol in leukemic cells through a combinatorial approach

Author(s)

LIU Wai M. ; SCOTT Katherine A. ; SHAMASH Jonathan ; JOEL Simon ; POWLES Thomas B. ;

Abstract

Δ9-Tetrahydrocannabinol (THC) is the active metabolite of cannabis, which has demonstrable cytotoxic activity in vitro.
In support of our previously published data, we have investigated the interactions between THC and anti-leukemia therapies and studied the role of the signalling pathways in mediating these effects.

Results showed clear synergistic interactions between THC and the cytotoxic agents in leukemic cells.

Additionally, exposure of cells to sub lethal levels of THC (1 μM) sensitised cells to these cytotoxic agents, by reducing IC50 values by ∼ 50%. Sensitisation appeared to be dependent upon the ability of THC to down regulate phosphorylated ERK, as cells dominantly expressive of MEK were not sensitised to the cytotoxic drugs by equi-molar amounts of THC.

Overall, these results demonstrate for the first time that a combination approach with THC and established cytotoxic agents may enhance cell death in vitro. Additionally the MAPK/ERK pathway appears responsible in part for these effects.

Journal Title

Leukemia & lymphoma    ISSN  1042-8194 

Source / Source

2008, vol. 49, no9, pp. 1800-1809 [10 page(s) (article)]

 

 


The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids

Br J Pharmacol. 2007 Nov;152(5):815-24. Epub 2007 Oct 1.

Source

The Discipline of Pharmacology, The University of Sydney, Sydney, New South Wales, Australia.

Abstract

BACKGROUND AND PURPOSE:

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter, P-glycoprotein in vitro.

Here we address the interaction of cannabinol (CBN), cannabidiol (CBD) and delta 9-tetrahydrocannabinol (THC) with the related multidrug transporter, ABCG2.

EXPERIMENTAL APPROACH:

Cannabinoid inhibition of Abcg2/ABCG2 was assessed using flow cytometric analysis of substrate accumulation and ATPase activity assays.

The cytotoxicity and chemosensitization by cannabinoids was determined with cell viability assays. Expression of cannabinoid and vanilloid receptors was assessed using reverse transcriptase polymerase chain reaction, and cannabinoid modulation of ABCG2 expression was examined using immunoblotting.

KEY RESULTS:

CBN, CBD and THC increased the intracellular accumulation of the Abcg2/ABCG2 substrate, mitoxantrone, in an over-expressing cell line.

The THC metabolite, (-)-11-nor-9-carboxy-delta 9-THC was much less potent.

The plant cannabinoids inhibited both basal and substrate stimulated ATPase activity of human ABCG2. Cannabinoid cytotoxicity occurred in the absence of known cannabinoid cell surface receptors, and only at concentrations higher than those required for Abcg2/ABCG2 inhibition.

Sub-toxic concentrations of the cannabinoids resensitized the overexpressing cell line to the cytotoxic effect of Abcg2/ABCG2 substrates, mitoxantrone and topotecan. This occurred in the absence of any effect on ABCG2 expression.

CONCLUSIONS AND IMPLICATIONS:

Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates.

PMID:
17906686
[PubMed - indexed for MEDLINE]

PMCID: PMC2190019

Free PMC Article

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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
MedicationDelta-9-THC

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.

 
 
Route(s)Oral
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
Full text 

Induction dose of propofol in patients using cannabis

Flisberg P, Paech MJ, Shah T, Ledowski T, Kurowski I, Parsons R 
Support, Non-U.S. Gov't]
Eur J Anaesthesiol 2009 Mar; 26(3):192-5.


BACKGROUND AND OBJECTIVE: An estimated 150 million people worldwide use cannabis.

The effect of cannabis on anaesthetic requirements in humans does not appear to have been studied.


METHODS: In this prospective, randomized, single-blinded study, 30 male patients using cannabis more than once per week (group C) and 30 nonusers (group NC), aged 18-50 years, were induced with propofol 1.5, 2, 2.5, 3 or 3.5 mg kg.

Additional doses were given when required. The primary outcome was the 50% effective dose of propofol and successful induction was determined by loss of consciousness with a bispectral index value of less than 60 and satisfactory insertion of a laryngeal mask. Propofol requirements to achieve these outcomes were recorded.


RESULTS: The dose required to achieve the target bispectral index value was not significantly higher in group C, but group C required a significantly higher propofol dose to achieve laryngeal mask insertion (314.0 +/- 109.3 vs. 263.2 +/- 69.5 mg, P < 0.04). The estimated effective propofol induction dose in 50-95% of patients did not significantly differ between groups.


CONCLUSION: We conclude that cannabis use increases the propofol dose required for satisfactory clinical induction when inserting a laryngeal mask.

More from this journalEuropean journal of anaesthesiolog

 


 

Smoking Pot, Cigarettes Ups COPD Risk

 
Study Shows Higher Risk for the Lung Disease Among Smokers of Both Marijuana and Tobacco
By Salynn Boyles
WebMD Health News
Reviewed by Louise Chang, MD
marijuana_tobacco_smoking_copd.jpg

April 13, 2009 -- People who smoke both cigarettes and marijuana have a greater risk for developing the progressive lung disease COPD than cigarette smokers who don't smoke pot, a new study shows.

Smokers in the study who reported using both tobacco and marijuana were three times as likely as nonsmokers to have clinically confirmed COPD (chronic obstructive pulmonary disease); people who smoked only cigarettes had a slightly lower risk.

The study is among the first to suggest a synergistic relationship between marijuana and tobacco use among older people who are most at risk for COPD.

"This effect suggests that smoking marijuana may act as a primer, or sensitizer, in the airways to amplify the adverse effects of tobacco on respiratory health," says study researcher Wan C. Tan, MD, of the University of British Columbia and St. Paul's Hospital in Vancouver, Canada.

COPD Risk

About 12 million Americans are currently living with a diagnosis of COPD; an equal number are believed to have the disease and not know it, according to the National Heart, Lung and Blood Institute.

In the U.S, the term COPD includes both emphysema and chronic bronchitis. With COPD, breathing becomes more difficult over time.

Largely caused by cigarette smoking, COPD is the fourth leading cause of death in the U.S.

While the link between tobacco and COPD is well established, far less is known about the impact of marijuana use on the lungs.

Some studies have found that even short-term heavy marijuana smoking can worsen lung function, while others have not shown this association.

Even less is known about the combined effects of smoking cigarettes and pot, Tan tells WebMD.

The study by Tan and colleagues included 878 residents of Vancouver, Canada participating in a larger investigation examining COPD prevalence.

Participants were considered tobacco smokers if they had smoked at least 365 cigarettes in their lifetime, and were considered marijuana smokers if they reported having ever smoked pot. The researchers defined "substantial" marijuana use as having smoked at least 50 marijuana cigarettes.

The average cigarette smoker in the study had smoked for 16 years, while the self-described pot smokers had smoked an average of 84 marijuana cigarettes.

When COPD was clinically confirmed though a diagnostic method known as spirometric testing:

  • The incidence of COPD among participants who smoked cigarettes alone was 2.7 times higher than among nonsmokers.
  • The incidence of COPD was 2.9 times higher among participants with a history of smoking both cigarettes and pot, even after controlling for other risk factors for the pulmonary disease.
  • COPD risk among people who smoked marijuana, but not tobacco, was slightly higher than among nonsmokers, but the increase was not statistically significant.

The study appears in the April 14 issue of the Canadian Medical Association Journal.

 


 
 

Probable Interaction Between Warfarin and Marijuana Smoking

Yamreudeewong W, Wong HK, Brausch LM, Pulley KR 
Probable Interaction Between Warfarin and Marijuana Smoking (July/August). [JOURNAL ARTICLE]
Ann Pharmacother 2009 Jun 16.

OBJECTIVE: To report a probable interaction between warfarin and marijuana smoking, resulting in increased international normalized ratio (INR) values and bleeding complications.


CASE SUMMARY: A 56-year-old white male had been receiving chronic warfarin therapy for 11 years after mechanical heart valve replacement. He was admitted to the hospital with a diagnosis of upper gastrointestinal bleeding. Upon admission, his INR value was supratherapeutic at 10.41, and his hemoglobin level was 6.6 g/dL.

He received 4 units of fresh frozen plasma and one 10-mg dose of oral vitamin K; his INR was 1.8 the next day. He was discharged 7 days after admission. Fifteen days after hospital discharge, he was readmitted with a constant nosebleed and increased bruising.

His INR value was 11.55. After treatment, he was discharged with an INR value of 1.14. The patient smoked marijuana more frequently throughout the period of these 2 hospitalizations due to his depression.

He was counseled by the pharmacist on the potential interaction of warfarin and marijuana. The patient decided to stop smoking marijuana after the third counseling session. During the 9 months that he did not smoke marijuana, his INR values ranged from 1.08 to 4.40 with no significant bleeding complications.


DISCUSSION: Marijuana may increase warfarin anticoagulant effect by inhibiting its metabolism, and to a lesser extent, displacing warfarin from protein-binding sites. Other causes (eg, nonadherence) of the patient's increased INR were ruled out. Using the Horn Drug Interaction Probability Scale, our patient's warfarin- marijuana interaction appeared to be probable.


CONCLUSIONS: To our knowledge, there have been no other reported cases of warfarin-marijuana interaction.

While more clinical reports would be useful to confirm this interaction, clinicians should be aware of its probability so as to manage patients appropriately.

The Annals of pharmacotherapy [Ann Pharmacother]

 

Cannabinoids, Opioids and MDMA: Neuropsychological Interactions Related to Addiction

 
Curr Drug Targets. 2010 Apr;11(4):429-39.

Source

Laboratori de Neurofarmacologia, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra and Institut Municipal d'Investigació Mèdica (IMIM), Barcelona, Spain. patricia.robledo@upf.edu

Abstract

3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an amphetamine derivative with psychostimulant properties.

This substance is widely used around the world by young adults in recreational settings. One of the most remarkable characteristic of ecstasy users is the concurrent consumption of several other drugs of abuse including psychostimulants, alcohol, tobacco, LSD, cannabis and opioids.

This poly-drug pattern of use is now prompting research towards understanding how the combination of MDMA with cannabis and opioids could affect neuropsychobiological processes related to addiction.

As with other drugs of abuse, behavioural evidence has been presented supporting the role of the endocannabinoid system as a modulator of the rewarding/reinforcing properties of MDMA.

On the other hand, the neurochemical substrate for the complex interactions between the endocannabinoid system and MDMA is poorly understood. MDMA also modulates the activity of the dynorphinergic and enkephalinergic systems in several brain structures related to addiction, as it has been shown for other psychostimulants.

The work regarding the contribution of micro- and delta-opioid receptors in the rewarding effects of MDMA shows differential results in pharmacological studies in rats, with respect to studies using knock-out mice. The present review describes the behavioural and neurochemical interactions between MDMA, cannabinoids and opioids with respect to addiction processes.

 

Cannabis coadministration potentiates the effects of "ecstasy" on heart rate and temperature in humans

Clin Pharmacol Ther. 2009 Aug;86(2):160-6. Epub 2009 May 13

Source

Department of Psychiatry, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen,

The Netherlands. g.j.h.dumont@psy.umcn.nl

Abstract

This study assessed the acute physiologic effects over time of (co)administration of Delta9-tetrahydrocannabinol (Delta9-THC) (the main psychoactive compound of cannabis) and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") in 16 healthy volunteers.

Pharmacokinetics and cardiovascular, temperature, and catecholamine responses were assessed over time. Both single-drug conditions robustly increased heart rate, and coadministration showed additive effects. MDMA increased epinephrine and norepinephrine concentrations, whereas THC did not affect the catecholamine response. Coadministration of MDMA and THC attenuated the increase of norepinephrine concentrations relative to administration of MDMA alone.

These results show that THC mediates heart rate increase independent of sympathetic (catecholaminergic) activity, probably through direct cannabinoid receptor type 1 (CB(1)) agonism in cardiac tissue.

Furthermore, THC coadministration did not prevent MDMA-induced temperature increase, but it delayed the onset and prolonged the duration of temperature elevation.

These effects may be of particular relevance for the cardiovascular safety of ecstasy users who participate in energetic dancing in nightclubs with high ambient temperature.

 

Interaction of the cannabinoid and opioid systems in the modulation of nociception

Int Rev Psychiatry. 2009 Apr;21(2):143-51

Source

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia 23298-0524, USA. swelch@vcu.edu

Abstract

Cannabinoids and opioids produce antinociceptive synergy.
 
Cannabinoids such as Δ-9-tetrahydrocannabinol (THC) release endogenous opioids and endocannabinoids such as anandamide (AEA) also alter endogenous opioid tone.
 
Opioids and cannabinoids bind distinct receptors that co-localize in areas of the brain involved with the processing of pain signals. Therefore, it is logical to look at interactions of these two systems in the modulation of both acute and chronic pain.
 
These drugs are often co-abused. In addition, the lack of continued effectiveness of opioids due to tolerance development limits the use of such drugs.
 
The cost to society and patients in terms of dollars, loss of productivity, as well as quality of life, is staggering.
 
This review summarizes the data indicating that with cannabinoid/opioid therapy one may be able to produce long-term antinociceptive effects at doses devoid of substantial side effects, while preventing the neuronal biochemical changes that accompany tolerance.
 
The clinical utility of modulators of the endocannabinoid system as a potential mimic for THC-like drugs in analgesia and tolerance-sparing effects of opioids is a critical future direction also addressed in the review.


Read More: http://informahealthcare.com/doi/abs/10.1080/09540260902782794

Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism

 
Br J Pharmacol. 1972 February; 44(2): 250–261.
 
PMCID: PMC1666020

Adolescent cannabis use increases risk for cocaine-induced paranoia

  
Author(s)Kalayasiri R, Gelernter J, Farrer L, Weiss R, Brady K, Gueorguieva R, Kranzler HR, Malison RT 
InstitutionDepartment of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
SourceDrug Alcohol Depend 2010 Mar 1; 107(2-3):196-201.
Abstract

Cannabis can produce and/or exacerbate psychotic symptoms in vulnerable individuals.

Early exposure to cannabis, particularly in combination with genetic factors, increases the risk of a subsequent, primary, psychotic disorder.

Because paranoia is a common feature of stimulant abuse and cocaine-dependent individuals frequently endorse a history of cannabis abuse, we examined whether early cannabis exposure, in conjunction with polymorphic variation in the catechol-O-methyl transferase gene (COMT Val158Met), influences the risk for cocaine-induced paranoia (CIP).


METHODS: Cannabis-use history was obtained in 1140 cocaine-dependent individuals from a family-based (affected sibling pair) study using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA).

Logistic regression and generalized estimating equations' analyses were used to examine the role of adolescent-onset cannabis use (< or =15 years of age) on CIP risk, both controlling for previously implicated CIP risk factors and familial relationships, and considering potential interactions with COMT Val158Met genotype.


RESULTS: Cocaine-dependent individuals who endorsed CIP had significantly higher rates of adolescent-onset cannabis use than those without CIP (62.2% vs. 50.2%; chi(2)=15.2, df=1, p<0.0001), a finding that remained after controlling for sibling correlations and other risk factors.

There were no effects of COMT genotype or genotype by early cannabis onset interactions. A modest (OR=1.4) and nearly significant (p=0.053) effect of CIP status in probands on CIP status in siblings was also noted.


CONCLUSIONS: Adolescent-onset cannabis use increases the risk of CIP in cocaine-dependent individuals. COMT genotype and its interaction with early cannabis exposure did not emerge as significant predictors of CIP. In addition, trait vulnerability to CIP may also be familial in nature.

  
Pub Type(s)Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PubMed ID

19944543

 

 
 

 

Induction dose of propofol in patients using cannabis

Flisberg P, Paech MJ, Shah T, Ledowski T, Kurowski I, Parsons R 
Research Support, Non-U.S. Gov't]
Eur J Anaesthesiol 2009 Mar; 26(3):192-5.

BACKGROUND AND OBJECTIVE:

An estimated 150 million people worldwide use cannabis. The effect of cannabis on anaesthetic requirements in humans does not appear to have been studied.


METHODS:

In this prospective, randomized, single-blinded study, 30 male patients using cannabis more than once per week (group C) and 30 nonusers (group NC), aged 18-50 years, were induced with propofol 1.5, 2, 2.5, 3 or 3.5 mg kg.

Additional doses were given when required. The primary outcome was the 50% effective dose of propofol and successful induction was determined by loss of consciousness with a bispectral index value of less than 60 and satisfactory insertion of a laryngeal mask.

Propofol requirements to achieve these outcomes were recorded.


RESULTS:

The dose required to achieve the target bispectral index value was not significantly higher in group C, but group C required a significantly higher propofol dose to achieve laryngeal mask insertion (314.0 +/- 109.3 vs. 263.2 +/- 69.5 mg, P < 0.04).

The estimated effective propofol induction dose in 50-95% of patients did not significantly differ between groups.


CONCLUSION:

We conclude that cannabis use increases the propofol dose required for satisfactory clinical induction when inserting a laryngeal mask.

 European journal of anaesthesiology