Tolerance, the capacity to consume larger amounts of cannabis without adverse effects and with diminishing sensitivity to the psychoactive effects has been established in chronic use. Patients who use copious amounts of cannabis on a daily basis commonly report that they do not experience the stronger psychoactive effects typical of casual use, a finding that has been verified by cognition and psychomotor testing. [1]

The establishment of a tolerance to cannabis was considered evidence of its addictive quality by early researchers. However, as early as 1981 some scientists had concluded that, “cannabis pharmacology suggests ways of minimizing tolerance and problems.” [2] Modern investigations of neuroscience, such as published by the National Institute of Mental Health (NIMH), indicate that the tolerance factor in cannabis use is entirely different from the tolerance established by classic addictive drugs.[3] While heroin addicts require increasing amounts of the drug to create similar effects, chronic cannabis users discover that marijuana’s psychoactive effects actually decrease with increasing amounts and frequency of use.

Tolerance to immune suppression is not well understood, yet has been observed. Australian National Health expert Peter Nelson explains:

The possibility of tolerance developing to any immunological effects of cannabinoids also make the human significance of the results of in vitro studies uncertain. If immunological tolerance develops with chronic use, then the possibility of observing even the small effects projected from the in vitro studies would be substantially reduced. Given the large number of cannabinoid effects to which tolerance has been shown to develop, it would not be surprising if this were also true of its immunological effects.[4]

While immunological tolerance is a matter of conjecture, the Institute of Medicine report, “Marijuana and Medicine,” offered a definitive determination on marijuana tolerance found in cerebral function. In short, according to the IOM: “The brain develops tolerance to cannabinoids.” [5]

Modern studies have isolated various factors and features of the tolerance factor both specific and non-uniform:

“Tolerance develops to many THC effects. Among them are behavioral actions, tachycardia, hypotension, effects on sex hormones, stimulation of prostaglandin E2 production, and inhibition of adynyl cyclase activity. Tolerance does not develop to all effects nor with the same speed and intensity. Tolerance to the tachycardic effects occur within a few days of continued useage. Administration of THC for a period of five days did not result in tolerance to the stimulating effects on adrenocorticotropin hormone (ACTH) secretion.

“O’Shaughnessy (1839) reported development of tolerance in connection with the medical use of tincture of “Indian hemp.” Two out of three cases of rheumatism showed good improvement, while the third patient did not respond to the therapy. Ultimately, the latter admitted to being “habituated to the use of the gunjah (cannabis) in the pipe.

“Tolerance to cannabinoid effects may occur due to pharmacodynamic changes (downregulation and internalization of receptors), or, to a lesser extent, due to pharmacokinetic changes (absorption, metabolism). Down regulation of cannabinoid receptors differs in distinct brain areas and corresponds to the resulting effects. Application of THC over a period of five days decreased specific receptor binding in different receptor sites of the brain ranging from 20 to 60 percent. Since tolerance does not develop to the actions of the acid metabolite THC-COOH (THC-11-oic-acid), some differences in tolerance for different effects may be due to additional non-receptor-mediated effects.” [6]

Related sections: Addiction, Cerebral Effects, Dependence, Psychoactivity, Psychomotor Skills, Toxicity.

[1] Jones, Benowitz, and Herning, “Clinical relavence of cannabis tolerance and dependence.” Journal of Clinical Pharmacology, (8-9 Suppl) p. 143S-152S, August 21, 1981

[2] Jones, Benowitz, and Herning, op. cit.

[3] Gettman, “The tolerance factor.” High Times, No. 239, July 1995/”Tolerance to cannabinoids.”

[4] “The health and psychological consequences of cannabis use.” Chapter 6, National Drug Strategy Mongraph, No. 25, Australia

[5] Institute of Medicine, Marijuana and Medicine, Assessing the Science Base. Washington, DC: National Academy Press, 1999

[6] Grotenhermen, Russo. Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential , pg. 62, New York: The Hawthorn Integrative Healing Press, 2002