Cannabinoids Pharmacology, Abuse, and Addiction

Abstract

Cannabis has a long history of therapeutic use and misuse. Δ-9-tetrahydrocannabinol (THC) was identified as the principle psychoactive component of cannabis in 1965. For the next two decades, cannabis research focused on THC pharmacology. Smoked or inhaled THC rapidly delivers the drug to the brain increasing its abuse liability. Once present in the brain THC hijacks important functions of the endogenous cannabinoid system modulating the release and reuptake of a wide variety of other neurotransmitters. THC disrupts memory, executive function, attention, hormone secretion, motor initiation and movement, decision-making, mood, and others. An individual using less than daily cannabis is considered an occasional user, while one who generally consumes the drug daily is considered a frequent cannabis user. The brain adapts to continuous CB1-cannabinoid receptor stimulation by reducing the density of receptors, but this can be reversed over weeks of sustained cannabis abstinence.

One of the major public health and safety considerations at this time of increasing cannabis medicalization and legalization is the effects on brain development in cannabis smokers that initiate use prior to the age of 17 years. The connections between different areas of the brain may not develop normally in these frequent adolescent cannabis smokers, and the changes in brain development may not be reversible. Another major public concern is the increased incidence of cannabis-impaired driving. Since the 1970s the incidence of drunk driving decreased, although it remains the major killer on the roads; however, drugged driving and, in particular, cannabis-impaired driving increased. The prevalence of THC in drivers’ blood or oral fluid increased 48 % between the 2007 and 2013–2014 National Roadside Surveys.

Importantly, individuals predisposed to develop schizophrenia or psychosis may have their condition exacerbated by cannabis intake and frequently may have their first schizophrenic break occur earlier following cannabis smoking. But the therapeutic potential of cannabinoids such as cannabidiol (CBD) or mixed THC and CBD plant extracts are currently being investigated to treat a wide variety of diseases. CBD has neuroprotective properties that are exploited as treatments for Davet’s syndrome, treatment resistant seizures in children refractory to other available therapies. The discovery of the cannabinoid receptors, CB1 and CB2, and identification of anandamide and other endogenous cannabinoids, improved our understanding of THC effects on the brain and mechanisms of cannabis addiction. Cannabis is addictive and is the principal drug of abuse for 75 % of 12–17 year olds seeking drug treatment. It is an exciting and concerning time for cannabis research. Potential new therapies for a wide variety of disorders co-occur with increased cannabis dependence and treatment demands, and concern over the long-term effects of frequent cannabis abuse in adolescents and the increased morbidity and mortality of cannabis-impaired driving.

The views in this chapter are those of the authors and do not necessarily represent those of the National Institute on Drug Abuse or the Department of Army.

Marilyn A. Huestis has retired from the National Institute on Drug Abuse and is currently at the University of Maryland School of Medicine, Baltimore, MD.