At the end of the 18th century, the first editions of American medical journals showed recommendations on hemp seeds and roots for the treatment of inflamed skin, incontinence and venereal diseases. The Irish doctor William O'Shaughnessy was the first to popularize the medical use of cannabis terpenes, also known as marijuana, in England and the United States. Medical cannabis, or medical marijuana, has become a widely discussed therapy in recent years. Controversies surrounding its legal, ethical and social implications; safe administration, packaging and dispensing; adverse health consequences and deaths attributed to marijuana poisoning; and therapeutic indications based on limited clinical data are some of the complexities associated with this treatment. Marijuana is currently recognized by the U.
S. Drug Enforcement Agency (DEA) as a Schedule I controlled substance, defined as having a high potential for abuse, no currently accepted medicinal use in treatment in the United States and the lack of accepted safety data for the use of treatment under medical supervision. This classification, combined with a national stigma surrounding potential harm and the implication of cannabis as a gateway drug to other substances, has been controversial. The United States Pharmacopoeia and the FDA have considered the complexities of regulating this plant-based therapy, including the numerous compounds and the complex interactions between substances in this product, and how it could fit into the current regulatory framework for drugs in the United States.
Many believe that the increase in interest in botanical medical cannabis is a side effect of the opioid abuse epidemic; public perception suggests that this plant-based therapy is seen as little different from a medicinal product or botanical supplement used for health or symptom relief if the disease persists. Advocates argue that there is evidence to support the use of botanical medical cannabis in the treatment of various conditions, especially when symptoms are resistant to treatment by other therapies; that there are beneficial cannabinoids, as evidenced by single-entity agents derived from cannabis containing THC and cannabidiol (CBD); that cannabis is relatively safe, with few deaths reported due to its use; that patients can self-evaluate their therapy; and that therapy is relatively inexpensive compared to pharmaceutical agents. Opponents of medical cannabis use argue, in part, that there is a lack of well-designed randomized trials to confirm benefits and harms; that it has not been subject to FDA approval process; that there is no standardization in potency or quantity of pharmacologically active components; that adverse health effects are related not only to smoking but also with unmasking mental health disorders, impaired coordination and impairment of judgment; that there is no standardization for packaging and controls to prevent inadvertent use by minors or pets; that there is a possibility of dependence, addiction and abuse; and that costs represent a potential burden. Regardless of personal opinions and perceptions, denying or ignoring the implications of cannabis use on patient health and health system infrastructure is irresponsible; physicians should be aware of these implications and informed about how this therapy can influence practice in a variety of healthcare settings, including intensive care.
The best-known endocannabinoid (eCB) ligands are N-arachidonyl-ethanolamide (anandamide or AEA) and sn-2-arachidonoylglycerol (2-AG). AEA and 2-AG are released on request from phospholipid precursors in cell membranes. This “classic” eCB system has expanded with the discovery of secondary receptors, ligands, and metabolic ligand enzymes. Compounds in environment include N-palmitlethanolamide (PEA), N-oleoylethanolamide (SEA) and cis-9-octadecenoamide (OEA or oleamide) which may represent a new way of molecular regulation of endogenous cannabinoid activity.
Other non-cannabinoid targets are also related to cannabis: G-protein-coupled receptors provide non-competitive inhibition in mu and delta opioid receptors, as well as norepinephrine, dopamine and serotonin; ligand-activated ion channels create allosteric antagonism in serotonin and nicotinic receptors and enhance glycine receptor activation; inhibition of calcium, potassium and sodium channels by non-competitive antagonism occurs in nonspecific ion channels; activation of PPARα and PPARgamma in peroxisome proliferator-activated receptors is influenced by AEA. The three most common methods of administration are inhalation through smoking, inhalation through vaporization, and ingestion of edible products. The method of administration may affect onset, intensity and duration of psychoactive effects; effects on organ systems; and addictive potential and negative consequences associated with consumption. Much of what is known about adverse effects of medical cannabis comes from studies with recreational marijuana users: Prolonged or intense use has caused short-term memory problems, motor coordination problems, impaired judgment, paranoia or psychosis at high doses; addiction; impaired brain development; cognitive impairment; poor educational outcomes; etc.
In randomized trials, average duration of exposure to cannabinoids was two weeks with an interval between eight hours and 12 months. Of patients assigned active treatment in these trials, 4779 were exposed to cannabinoids.
