Tolerance cannabis

Jones RT, Benowitz N (1976) The 30-day trip—clinical studies of cannabis tolerance and dependence. In Braude MC, Szara S (eds) Pharmacology of Marihuana. Raven Press, New York, pp 627-642... 

Jones RT, Benowitz NL, Herning Rl (1981) Clinical relevance of cannabis tolerance and dependence. J Clin Pharmacol 21 143S-152S... 

Teesson M, Lynskey M, Manor B, et al The psychometric properties of BSM-IV cannabis use disorders. Brug Alcohol Bepend 68 235—262, 2002 Tsou K, Patrick SL, Walker JM. Physical withdrawal in rats tolerant to delta 9-tetrahydrocannabinol precipitated by a cannabinoid receptor antagonist. Eur J Pharmacol 280 R13-R15, 1995... 

Given the low incidence of severe withdrawal symptoms and the modest effects on the mesolimbic dopamine (reward) system, most investigators have found that cannabis has a low abuse or addiction potential. However, it has been argued that if cannabis is a non-addictive substance, why is its use so widespread and why are there so many longterm and heavy users Finally, contrary to the evidence that cannabis can produce chronic tolerance, some regular users report that they require less drug to achieve the same high, or sensitisation (Chapter 3). Three possible explanations may account for this. First, chronic users may focus on the effects that they wish to achieve. Second, the... 

A comprehensive study by Wert and Raulin (1986) examined both American and cross-cultural studies, and pointed out methodological problems in the body of research on cannabis. It was concluded that cannabis use may produce subtle impairment, but there is no evidence that cannabis produces gross structural cerebral changes or functional impairment. Many cannabis users remain intelligent, functional, and productive members of society (Grinspoon 1999 Davidson 1999). Tolerance, Dependence, and Addiction... 

In mice, somatic signs of withdrawal include wet dog shakes, front paw tremor, ataxia, hunched posture, tremor, ptosis, piloerection, mastication and decreased locomotor activity (Hutcheson et al. 1998). The CBl antagonist (SR141716A) has been used to precipitate a withdrawal state in THC-tolerant animals, and higher doses of THC produced a greater withdrawal syndrome (Aceto et al. 1995 Cook et al. 1998). Withdrawal from chronic cannabis use reduces mesolimbic dopaminer-... 

The effects of cannabis on seizures is, at best, unpredictable. Although some cannabinoids have antiseizure effects, tolerance rapidly develops. Further, rebound hyperexcitability following THC administration may render these benefits impractical. Indeed, cannabinoids facilitate seizures and kindling in many studies. Certain isolated cannabinoids may eventually prove useful for treating seizures, but cannabis as a whole is not effective. In light of this, individuals with epilepsy are strongly recommended to avoid cannabis. 

Tolerance develops to many of A -THC s effects in heavy marijuana users. Although chronic cannabis use does not result in severe withdrawal symptoms, numerous case reports attest to development of dependence in subjects taking high doses of THC for several weeks. The most prominent symptoms were irritability and restlessness others included insomnia, anorexia, increased sweating, and mild nausea. Cessation of mild or moderate use of marijuana, however, does not produce a withdrawal syndrome. 

Brain cannabinoid receptor. In humans, psychoactive cannabinoids produce euphoria, enhancement of sensory perception, tachycardia, antinociception, difficulties in concentration, and impairment of memory. The cognitive deficiencies persist after withdrawal. The toxicity of cannabis has been underestimated for a long time, since recent findings revealed that A-9-THG-induced cell death with shrinkage of neurons and DNA fragmentation in the hippocampus. The acute effects of cannabinoids, as well as the development of tolerance, are mediated by G protein-coupled cannabinoid receptors. The CBl receptor and its splice variant, CBl A, are found predominantly in the brain with highest densities in the hippocampus, cerebellum, and striatum. The CB2 receptor is found predominantly in the spleen and in hemopoi-... 

Dyskinetic activity. A 4-week dose escalation study was performed to assess the safety and tolerability of cannabis in six patients with Parkinson s disease (PD) with levodopa (L-DOPA)-induced dyskinesia. 

P. Jobin, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis a randomized, double-blind, placebo-controlled, crossover study. 

In this book there have not been systematic examinations of the conceptual status and details of dependent states on the various drugs, but it is certainly worth noting that a condition comprising true dependence on cannabis is now recognized. In many ways the three cardinal features of dependence on a substance are tolerance, craving and withdrawal symptoms, and these have clearly been shown particularly in users presenting for treatment. 

A9-Tetrahydrocannabinol is the major psychoactive cannabinoid in marijuana (Cannabis sativa). Its synthetic form, dronabinol, became available in the U.S. in 1985 as an antiemetic for patients receiving emetogenic chemotherapy. However, it is seldom used as a first-line antiemetic because of its psychoactive effects, and its use is usually limited to patients who have a low tolerance or minimal response to other antiemetic drugs (see Chapter 18). 

Tolerance to the effects of marijuana clearly exist even though chronic users have described a reversed tolerance and claim that smaller doses of the drug are necessary to produce the desired effects. This effect is probably related to the manner of use and the expectations of the user. Chronic, high-dose cannabis users may experience an abstinence or withdrawal syndrome on abrupt discontinuation of use. Signs and symptoms include irritability, restlessness, nervousness, weight loss, insomnia, and rapid eye movement (REM) rebound. Onset of this syndrome is several hours after the last dose, and it lasts 4 to 5 d. Because withdrawal is not life-threatening, treatment involves little more than supportive therapy with short-term, low doses of benzodiazepines. 

Eating or smoking marijuana has been shown to increase heart rate by 20 to 50 percent. This effect can occur within a few minutes to a quarter of an hour and can last for up to three hours. Because of the brain s tolerance to THC, it has been shown that these effects are temporary. However, marijuana users who do not know about or expect these acute health effects may find them unpleasant or even scary, resulting in panic or anxiety reactions. And, those with heart problems or other physical disorders may have disturbing or even harmful effects as a result of cannabis use. 

Regular use of cannabis can lead to an intake of THC which would be toxic to the naive user. This suggests that tolerance develops. While there is some evidence that metabolic tolerance may arise, it would appear that tissue... 

A9-tetrahydrocannabinol, the active component in herbal cannabis, is very safe. Laboratory animals (rats, mice, dogs, monkeys) can tolerate doses of up to 1000 mg/kg, equivalent to some 5000 times the human intoxicant dose. Despite the widespread illicit use of cannabis, there are very few, if any, instances of deaths from overdose (9). 

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