Tag Archives: THC

Adverse effects of cannabis. (2011)

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Abstract

“Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user’s knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to establish a causal relationship in either direction, because of these methodological limitations. In Australia, the marked increase in cannabis use has not been accompanied by an increased incidence of schizophrenia. On the basis of the available data, we cannot reach firm conclusions on whether or not cannabis use causes psychosis. It seems prudent to inform apparently vulnerable individuals that cannabis may cause acute psychotic decompensation, especially at high doses. Users can feel dependent on cannabis, but this dependence is usually psychological. Withdrawal symptoms tend to occur within 48 hours following cessation of regular cannabis use, and include increased irritability, anxiety, nervousness, restlessness, sleep difficulties and aggression. Symptoms subside within 2 to 12 weeks. Driving under the influence of cannabis doubles the risk of causing a fatal road accident. Alcohol consumption plays an even greater role. A few studies and a number of isolated reports suggest that cannabis has a role in the occurrence of cardiovascular adverse effects, especially in patients with coronary heart disease. Numerous case-control studies have investigated the role of cannabis in the incidence of some types of cancer. Its role has not been ruled out, but it is not possible to determine whether the risk is distinct from that of the tobacco with which it is often smoked. Studies that have examined the influence of cannabis use on the clinical course of hepatitis C are inconclusive. Alcohol remains the main toxic agent that hepatitis C patients should avoid. In practice, the adverse effects of low-level, recreational cannabis use are generally minor, although they can apparently be serious in vulnerable individuals. The adverse effects of cannabis appear overall to be less serious than those of alcohol, in terms of neuropsychological and somatic effects, accidents and violence.”

http://www.ncbi.nlm.nih.gov/pubmed/21462790

Cannabis–1988.

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Abstract

“In this updating review of research on cannabis particular attention has been paid to the increasing number of studies of the disposition of the components of cannabis in man, as well as possible effects on health. Specific binding sites for cannaboids have not been demonstrated. Approximately 80 metabolites of tetrahydrocannabiol (THC) have been discovered, of which 11-OH-THC is the main metabolite, but it contributes little to the overall effect when the drug is smoked or given intravenously. The minimum plasma level of THC associated with the psychotropic effect is 25 ng/ml. Cannabis may produce directly an acute panic reaction, a toxic delirium, and acute paranoid state, or acute mania. Cannabis use may aggrevate schizophrenia, but it is much less certain whether it can lead to sociopathy or even to “amotivational syndrome”. Despite widespread use of cannabis in virtually all parts of the world, no catastrophic effects on health have been noted. Cannabis appears to be relatively safe as compared with current social drugs. It is, however, still too early in the history of the present episode of cannabis use to be sanguine about possible bad effects.”

http://www.ncbi.nlm.nih.gov/pubmed/2852450

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/

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

Central and peripheral mechanisms contribute to the antiemetic actions of delta-9-tetrahydrocannabinol against 5-hydroxytryptophan-induced emesis.

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Abstract

“Delta-9-tetrahydrocannabinol (delta-9-THC) prevents cisplatin-induced emesis via cannabinoid CB(1) receptors. Whether central and/or peripheral cannabinoid CB(1) receptors account for the antiemetic action(s) of delta-9-THC remains to be investigated. The 5-hydroxytryptamine (5-HT=serotonin) precursor, 5-hydroxytryptophan (5-HTP), is an indirect 5-HT agonist and simultaneously produces the head-twitch response (a centrally mediated serotonin 5-HT(2A) receptor-induced behavior) and emesis (a serotonin 5-HT(3) receptor-induced response, mediated by both peripheral and central mechanisms) in the least shrew (Cryptotis parva). The peripheral amino acid decarboxylase inhibitor, carbidopa, prevents the conversion of 5-HTP to 5-HT in the periphery and elevates 5-HTP levels in the central nervous system (CNS). When administered i.p. alone, a 50 mg/kg dose of 5-HTP failed to induce either behaviour while its 100 mg/kg dose produced robust frequencies of both head-twitch response and emesis. Pretreatment with carbidopa (0, 10, 20 and 40 mg/kg) potentiated the ability of both doses of 5-HTP to produce the head-twitch response in a dose-dependent but bell-shaped manner, with maximal potentiation occurring at 20 mg/kg carbidopa. Carbidopa dose-dependently reduced the frequency of 5-HTP (100 mg/kg)-induced emesis, whereas the 10 mg/kg dose potentiated, and the 20 and 40 mg/kg doses suppressed the frequency of vomits produced by the 50 mg/kg dose of 5-HTP. The peripheral and/or central antiemetic action(s) of delta-9-THC (0, 1, 2.5, 5, 10 and 20 mg/kg) against 5-HTP (100 mg/kg)-induced head-twitch response and emesis were investigated in different groups of carbidopa (0, 10 and 20 mg/kg) pretreated shrews. Irrespective of carbidopa treatment, delta-9-THC attenuated the frequency of 5-HTP-induced head-twitch response in a dose-dependent manner with similar ID(50) values. Although delta-9-THC also reduced the frequency of 5-HTP-induced emesis with similar ID(50s), at the 5 mg/kg delta-9-THC dose however, 5-HTP induced significantly less vomits in the 10 and 20 mg/kg carbidopa-treated groups relative to its 0 mg/kg control group. Moreover, increasing doses of carbidopa significantly shifted the inhibitory dose-response effect of delta-9-THC in protecting shrews from 5-HTP-induced emesis to the left. Relatively, a large dose of delta-9-THC (20 mg/kg) was required to significantly reduce the number of vomits produced by direct acting serotonergic 5-HT(3) receptor agonists, serotonin and 2-methylserotonin. Low doses of delta-9-THC (0.1-1 mg/kg) nearly completely prevented 2-methylserotonin-induced, centrally mediated, head-twitch and ear-scratch responses. The results indicate that delta-9-THC probably acts pre- and postsynaptically to attenuate emesis produced by indirect and direct acting 5-HT(3) receptor agonists via both central and peripheral mechanisms. In addition, delta-9-THC prevents 5-HTP-induced head-twitch and emesis via cannabinoid CB(1) receptors since the CB(1) receptor antagonist, SR 141716A [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide], countered the inhibitory actions of an effective dose of delta-9-THC against both behaviours.”

http://www.ncbi.nlm.nih.gov/pubmed/15044052

http://www.thctotalhealthcare.com/category/nauseavomiting/

Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew.

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“The present study investigates the cannabinoid receptor mechanisms by which Delta(9)-THC produces its antiemetic effects against cisplatin -induced emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew.

Intraperitoneal administration of Delta(9)-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals vomiting (ID(50)=1.8+/-1.6 mg/kg) and the frequency of vomits (ID(50)=0.36+/-1.18 mg/kg) in a potent manner.

The lowest significantly effective antiemetic dose of Delta(9)-THC for the latter emesis parameters was 2.5 mg/kg. Although Delta(9)-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from vomiting (80% protection). The cannabinoid CB(1) antagonist (SR 141716A) and not the CB(2) antagonist (SR 144528), reversed the antiemetic effects of Delta(9)-THC in a dose-dependent fashion. Delta(9)-THC (1, 5, 10 and 20 mg/kg, ip) suppressed locomotor parameters (spontaneous locomotor activity, duration of movement and rearing frequency) in a biphasic manner and only the 20-mg/kg dose simultaneously suppressed the triad of locomotor parameters to a significant degree. Subcutaneous (1-10 mg/kg) and intraperitoneal (0.05-40 mg/kg) injection of some doses of SR 141716A caused significant reductions in one or more components of the triad of locomotor parameters but these reductions were not dose dependent. Subcutaneous injection of SR 141716A (0.2, 1, 5 and 10 mg/kg) reversed the motor suppressant effects of a 20-mg/kg dose of Delta(9)-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects,

Delta(9)-THC is a more potent antiemetic agent. Both effects are probably mediated via CB(1) receptors in distinct loci.”

http://www.ncbi.nlm.nih.gov/pubmed/11420092

http://www.thctotalhealthcare.com/category/nauseavomiting/