- Pharmacology and Toxicology
Pharmacology and Toxicology
TOXICOLOGY OF CANNABIS
Cannabinoids have demonstrated a promising safety profile as both THC and CBD demonstrate low toxicity both in short and long term use. To date, there has been zero evidence to support a death caused exclusively from a cannabis overdose(42).
Currently there may lack applicability of available research regarding chronic effects of cannabis use. Although recreational use of cannabis is done primarily one via inhalation, the majority of clinical studies that investigate medical cannabis are done through administration via means other than smoking (ex. capsules, sprays). With this, it is estimated that the lethal dose of THC when administered intravenously is 30 mg/kg of body weight (3). While research is working toward elucidating the effects of long-term cannabis use in humans, it has been demonstrated to be relatively well tolerated in animals without serious deterioration in general health. Some mild effects, however, include increased heart rate, reddened eyes, a dry mouth, and psychoactive effects including mild euphoria, enhanced sensory perception, fatigue, dysphonia and anxiety(3).
Smoking cannabis during pregnancy is linked to lower birth weight in the offspring; the relationship between smoking cannabis during pregnancy and other pregnancy and childhood outcomes is unclear(42). There have been several studies on the effect of cannabis use on hepatitis C-related liver fibrosis, but the results have been mixed(42). While acute exposure to cannabis results in increased heart rate, chronic exposure is associated with bradycardia and hypotension, cannabis use is not associated with lung, head and neck cancers; but is associated with testicular cancer(42, 43). Adverse neuropsychological effects (learning, memory) has also been associated with long-term and early onset cannabis use(42, 43).
The potential toxic effects of CBD specifically have been extensively reviewed(44) with a recent update of the literature (44, 45). The following are some of the relevant findings to date from in vitro and animal studies:
- CBD affects growth of tumoral cell lines but has no effect in most non-tumour cells. However, a pro-apoptotic effect has been observed in lymphocytes.
- CBD has no effect on embryonic development (limited research).
- Evidence on potential hormonal changes is mixed with some evidence of possible effects, and other studies suggesting no effect, depending on the method used and the hormone studied.
- CBD has no effect on a wide range of physiological and biochemical parameters or has significant effects on animal behaviour unless extremely high doses are administered (e.g., more than 150 mg/kg iv as an acute dose or more than 30 mg/kg orally daily for 90 days in monkeys)
- Effects on the immune system are unclear; there is evidence of immune suppression at higher concentrations, but immune stimulation may occur at lower concentrations.
- There is potential for CBD to be associated with drug interactions through inhibition of some cytochrome P450 enzymes, but it is not yet clear whether these effects occur at physiological concentrations.
THE MEDICAL CANNABIS FUTURE
As more research and clinical studies pave a way towards a better and more regulated use of medical cannabis in terms of safety and quality, more medical practitioners will understand and start the use of medical cannabis in their regular prescriptions. This could be a massive step towards ending the opioid crisis in the country. In the coming years, the systematic approach to research would help ensure that our approach to the use of medical cannabis is guided by sound evidence and not anecdotal evidence. There is a definite need for more clinical studies to clearly elucidate the mechanisms behind the vast range of effects of various cannabinoids in our body(6). More information about the mechanism and toxicological aspects of individual cannabinoids will lead to a much more efficient and safer drug therapy catered to individual needs and genetic predisposition.