The safety profile of smoked Cannabis, based on the ratio of therapeutic to lethal dose, is excellent. There is no established lethal dose or record in the medical literature of a Cannabis-induced fatality. In contrast, many commonly prescribed and abused substances such as barbiturates, opiates, and benzodiazepines have a more narrow therapeutic window and can be lethal in overdose. Adverse effects of cannabis include anxiety attacks and cognitive impairment.
Dependence to cannabis has been reported in 9% of regular users, but withdrawal symptoms are mild and self-limiting. A recent study published in the Journal of the American Medical Association, one of the leading biomedical journals, found that long-term exposure to cannabis smoke was not associated with adverse effects on pulmonary function, in a large cohort of over 5000 men and women over a 20-year period.
Efficacy and Synthetic Marijuana
Marijuana has been used for medicinal properties for centuries, but a complicated federal approval process has limited modern research. The American College of Physicians has called for increased research into the therapeutic role of medical marijuana, reclassification of the drug from the Schedule I level, and exemption from federal criminal prosecution for physicians who prescribe or dispense medical marijuana in accordance with state law.
Medical benefit for use of the synthetic marijuana extracts is well-established and less inhibited by regulations. In the human body, different cellular receptors exist that respond to different cannabinoid molecules; susceptibility varies among humans. The cannabinoid-1 (CB1) receptors may modulate psychoactive properties, while CB2 receptors may provide anti-inflammatory or regenerative benefits. The synthetic delta-9-tetrahydrocannabinol (THC), dronabinol (trade name Marinol), was approved by the FDA in 1992, and the synthetic analog Nabilone was approved in 1985, for therapeutic uses as an antiemetic and as an adjunct analgesic for neuropathic pain. Recent studies of the liquid marijuana extract Sativex, which contains a mixture of THC and cannabidiol (CBD), have lead to its approval in Canada, New Zealand, and several European countries. Phase III trials of Sativex for the treatment of pain associated with cancer are underway in the US.