Reinforcing properties of oral delta 9-tetrahydrocannabinol, smoked marijuana, and nabilone: influence of previous marijuana use.

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Abstract

“The reinforcing properties of delta 9THC (17.5 mg), a 1 g marijuana cigarette containing 1.83% delta 9-THC, a synthetic cannabis compound (Nabilone 2 mg orally), and their respective placebos were assessed with self-report and operant work-contingent choice procedures. Three groups of eight subjects were selected on the basis of a history of regular, intermittent, or occasional marijuana-smoking behavior. All subjects served as their own controls for each drug condition and studies were carried out under double-blind and “double-dummy” conditions in a controlled, residential research ward. Placebo responding did not vary as a function of history of marijuana use, but the past history of drug use had a significant influence on the reinforcing properties of cannabis compounds as well as the behavioral and physiological effects of these drugs. Regular marijuana users reported a significant increase in elation following marijuana smoking, but this was not associated with a significant increment in pulse rate. Intermittent and occasional marijuana smokers had significant increases in pulse rate, but no significant marijuana-induced elation. Nabilone and delta 9-THC produced a significant increase in pulse rate for all subject groups, but there was no significant increase in elation following ingestion of these compounds. Given a choice between the three drugs and three placebos, 18 of 23 subjects worked to obtain a marijuana cigarette in an operant work choice paradigm. These data indicate that smoked marijuana was significantly more reinforcing than all other cannabis compounds studied, regardless of past drug-use history.”

http://www.ncbi.nlm.nih.gov/pubmed/6149589

Reinforcing and subjective effects of oral delta 9-THC and smoked marijuana in humans.

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Abstract

“The reinforcing and subjective effects of oral delta-9-tetrahydrocannabinol (THC) and smoked marijuana were studied in two groups of regular marijuana users. One group (N = 10) was tested with smoked marijuana and the other (N = 11) with oral THC. Reinforcing effects were measured with a discrete-trial choice procedure which allowed subjects to choose between the self-administration of active drug or placebo on two independent occasions. Subjective effects and heart rate were measured before and after drug administration. Smoked active marijuana was chosen over placebo on both choice occasions by all subjects. Similarly, oral THC was chosen over placebo on both occasions by all but one subject. Both active drug treatments produced qualitatively and quantitatively similar subjective effects, and both significantly increased heart rate, although the time course of effects differed substantially between the two treatments. The results demonstrate that both smoked marijuana and oral THC can serve as positive reinforcers in human subjects under laboratory conditions. The experimental paradigm used here should prove useful for identifying factors that influence the self-administration of marijuana and other cannabinoids by humans.”

http://www.ncbi.nlm.nih.gov/pubmed/1319601

Substitution profile of the cannabinoid agonist nabilone in human subjects discriminating δ9-tetrahydrocannabinol.

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Abstract

“OBJECTIVES:

The central effects of Δ-tetrahydrocannabinol (Δ-THC), the primary active constituent of cannabis, are attributed to cannabinoid CB1 receptor activity, although clinical evidence is limited. Drug discrimination has proven useful for examining the neuropharmacology of drugs, as data are concordant with the actions of a drug at the receptor level. The aim of this study was to determine the profile of behavioral and physiological effects of the cannabinoid agonist nabilone in humans trained to discriminate Δ-THC.

METHODS:

Six cannabis users learned to identify when they received oral Δ-THC (25 mg) or placebo and then received a range of doses of the cannabinoid agonists nabilone (1, 2, 3, and 5 mg) and Δ-THC (5, 10, 15, and 25 mg). The dopamine reuptake inhibitor methylphenidate (5, 10, 20, and 30 mg) was included as a negative control. Subjects completed the Multiple-Choice Procedure, and self-report, task performance, and physiological measures were collected.

RESULTS:

Nabilone shared discriminative-stimulus effects with the training dose of Δ-THC, produced subject-rated drug effects that were comparable to those of Δ-THC, and increased heart rate. Methylphenidate did not engender Δ-THC-like discriminative-stimulus effects.

CONCLUSIONS:

These data demonstrate that the interoceptive effects of nabilone are similar to Δ-THC in cannabis users. The overlap in their behavioral effects is likely due to their shared mechanism as CB1 receptor agonists. Given the relative success of agonist replacement therapy to manage opioid, tobacco, and stimulant dependence, these results also support the evaluation of nabilone as a potential medication for cannabis-use disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/20838217

Separate and combined effects of the cannabinoid agonists nabilone and Δ9-THC in humans discriminating Δ9-THC

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“Background

Agonist replacement treatment is a promising strategy to manage cannabis-use disorders. The aim of this study was to assess the combined effects of the synthetic cannabinoid agonist nabilone and Δ9-tetrahydrocannabinol (Δ9-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ9-THC was also conducted to provide initial safety and tolerability data, which is important because cannabis users will likely lapse during treatment.”

“Conclusions

These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis. These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089804/

Nabilone: an effective antiemetic in patients receiving cancer chemotherapy.

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Abstract

“Eighty evaluable patients receiving chemotherapy were entered on a random prospective double-blind study to evaluate the effectiveness of nabilone, a synthetic cannabinoid, compared to prochlorperazine. Most of these patients received cisplatin, a drug that universally produces severe nausea and vomiting, as part of a combination chemotherapy regimen. The patients served as their own controls, receiving either nabilone or prochlorperazine during two consecutive treatment courses with the identical chemotherapy. Side effects consisting of hypotension and lethargy were more pronounced with nabilone. Toxicity, in general, did not preclude antiemetic treatment and in no way interfered with chemotherapy. Sixty patients (75 per cent) reported nabilone to be more effective than prochlorperazine for relief of nausea and vomiting. Of these 60 patients, 46 required further chemotherapy and continued taking nabilone as the antiemetic of choice.”

http://www.ncbi.nlm.nih.gov/pubmed/6271844

Nabilone. A preliminary review of its pharmacological properties and therapeutic use.

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Abstract

“Nabilone is a new orally active cannabinoid for the treatment of severe gastrointestinal toxicity associated with cancer chemotherapy. The pharmacological profile of nabilone suggests that it acts primarily by preventing emesis controlled by the medulla oblongata, although its secondary mild anxiolytic activity may contribute to the overall efficacy. Nabilone 2mg twice daily starting 12 hours prior to, and continued for the duration of, chemotherapy produces significant reduction in the severity and duration of nausea and the frequency of vomiting in about 50 to 70% of patients with severe symptoms refractory to conventional therapy. Nabilone has proven to be more effective in controlling symptoms and preferred by more patients than prochlorperazine 10mg 2 to 4 times daily in a limited number of studies, despite a higher incidence of side effects. Comparative trials against other new antiemetic agents, such as high dose metoclopramide, and use of nabilone in combination with other antiemetics remain to be undertaken. The incidence of side effects is high with nabilone; drowsiness, dizziness and/or vertigo occur in 60 to 70% of patients, but rarely lead to drug withdrawal, although more troublesome effects, such as postural hypotension, ataxia, vision disturbance and toxic psychoses, may cause discontinuation of therapy. Thus, nabilone offers an effective alternative to the treatment options available in a difficult therapeutic area – those patients with severe gastrointestinal side effects from cancer chemotherapy who are refractory to conventional therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/2863127

Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy.

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Abstract

“Nabilone, a synthetic cannabinoid, and Prochlorperazine were compared in a double-blind crossover study of 34 patients with lung cancer undergoing a 3-day schedule of chemotherapy with Cyclophosphamide, Adriamycin and Etoposide. Symptom scores were significantly better for patients on nabilone for nausea, retching and vomiting (P less than 0.05). Fewer subjects vomited with nabilone (P = 0.05) and the number of vomiting episodes was lower (P less than 0.05); no patients on nabilone required additional parenteral anti-emetic. More patients preferred nabilone for anti-emetic control (P less than 0.005). Adverse effects common with nabilone were drowsiness (57%), postural dizziness (35%) and lightheadedness (18%). Euphoria was seen in 14% and a “high” in 7%. Erect systolic blood pressure was lower in nabilone patients on Day 1 (P = 0.05) but postural hypotension was a major problem in only 7%. Nabilone is an effective oral anti-emetic drug for moderately toxic chemotherapy, but the range and unpredictability of its side-effects warrant caution in its use.”

http://www.ncbi.nlm.nih.gov/pubmed/6315040

Recent advantages in cannabinoid research.

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Abstract

“Although the active component of cannabis Delta9-THC was isolated by our group 35 years ago, until recently its mode of action remained obscure. In the last decade it was established that Delta9-THC acts through specific receptors – CB1 and CB2 – and mimics the physiological activity of endogenous cannabinoids of two types, the best known representatives being arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG). THC is officially used against vomiting caused by cancer chemotherapy and for enhancing appetite, particularly in AIDS patients. Illegally, usually by smoking marijuana, it is used for ameliorating the symptoms of multiple sclerosis, against pain, and in a variety of other diseases. A synthetic cannabinoid, HU-211, is in advanced clinical tests against brain damage caused by closed head injury. It may prove to be valuable against stroke and other neurological diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/10575284

Marijuana as antiemetic medicine: a survey of oncologists’ experiences and attitudes.

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Abstract

“A random-sample, anonymous survey of the members of the American Society of Clinical Oncology (ASCO) was conducted in spring 1990 measuring the attitudes and experiences of American oncologists concerning the antiemetic use of marijuana in cancer chemotherapy patients. The survey was mailed to about one third (N = 2,430) of all United States-based ASCO members and yielded a response rate of 43% (1,035). More than 44% of the respondents report recommending the (illegal) use of marijuana for the control of emesis to at least one cancer chemotherapy patient. Almost one half (48%) would prescribe marijuana to some of their patients if it were legal. As a group, respondents considered smoked marijuana to be somewhat more effective than the legally available oral synthetic dronabinol ([THC] Marinol; Unimed, Somerville, NJ) and roughly as safe. Of the respondents who expressed an opinion, a majority (54%) thought marijuana should be available by prescription. These results bear on the question of whether marijuana has a “currently accepted medical use,” at issue in an ongoing administrative and legal dispute concerning whether marijuana in smoked form should be available by prescription along with synthetic THC in oral form. This survey demonstrates that oncologists’ experience with the medical use of marijuana is more extensive, and their opinions of it are more favorable, than the regulatory authorities appear to have believed.”

http://www.ncbi.nlm.nih.gov/pubmed/2045870

Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT(1A) receptor activation.

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“BACKGROUND AND PURPOSE:

To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5-HT(1A) receptor activation in animal models.”

“CONCLUSIONS AND IMPLICATIONS:

Compared to cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5-HT(1A) receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.”

http://www.ncbi.nlm.nih.gov/pubmed/23121618