The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD). A literature search was performed in the bibliographic databases PubMed, PsycINFO, and Web of Science using the keyword “cannabidiol.” After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone’s individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users.
Tetrahydrocannabinol (THC) is the main psychoactive substance in cannabis. Cannabidiol (CBD) is a cannabinoid that appears in cannabis resin but rarely in herbal cannabis. In recent years, many positive attributes have been ascribed to CBD. Is cannabis that contains CBD less harmful than cannabis without CBD? Are people who smoke cannabis resin, therefore, less susceptible to psychosis or less likely to become addicted than are people who smoke herbal marijuana? In this article, several of the health aspects of CBD will be reviewed. The article will focus on the role played by CBD in contributing to the psychological effects that are experienced during recreational cannabis use.
Toxicology of CBD
Research on the pharmacological and toxicological properties of CBD has been performed on different types of animals. In general, the metabolism of CBD in different species seems similar to that observed in humans, but some differences exist (26). It is possible that differences in metabolism and kinetics among different species have been responsible for some of the observed differences in pharmacological and toxicological effects.
Little research has focused on the safety and side effects of CBD in humans. However, several studies have described the effects of CBD for therapeutic applications in clinical trials. Only a few, generally mild side effects have been observed after administration of CBD in these human studies, though a wide range of effects over a wide dose range, including acute and chronic administration, have been examined. Few undesirable effects are reported, and tolerance for CBD does not seem to occur.
Based on an extensive literature review, Bergamaschi and colleagues concluded that CBD, to the extent that it has been studied, is a substance with low toxicity (27). Notably, however, the absence of harmful effects of CBD in humans has been described in research that was not primarily aimed at investigating these same side effects or toxicities of CBD. Because no specific research on these issues has been performed, it is currently impossible to draw conclusions about differences in toxicity between hashish and marijuana.
Chronic cannabis use is associated with psychiatric toxicity and cannabis has been implicated in the etiology of long-term psychiatric conditions (28). Several in vivo brain scanning techniques have been conducted to investigate whether chronic, heavy cannabis use leads to structural changes in the brain [for reviews, see Ref. (29, 30)]. The results of these studies have been relatively inconsistent. In general, no differences in total brain volume between cannabis users and non-users have been found. With respect to CB1 receptor concentrations in different parts of the brain, it can be expected that structural changes after chronic intensive cannabis use would most likely eventually be situated in the orbitofrontal cortex (OCC), the anterior cingulate cortex (ACC), the striatum, the amygdala, and the hippocampus (31–33). In some structural magnetic resonance imaging (sMRI) studies, reductions in the volumes of the hippocampus, the amygdala, and the cerebellum have been found in adult heavy cannabis users when compared with healthy controls (21, 34, 35). Using a PET scan technique, Wilson and colleagues found age-dependent morphological changes in early-onset cannabis users. In subjects who started their cannabis use before the age of 17, it has been found that the ratio of cortical gray to white matter is smaller when compared with subjects who had started using cannabis after their 17th birthdays (36). Structural abnormalities due to chronic cannabis use have been most consistently identified in the hippocampus (21, 34, 35). Using a voxel-based morphometry (VBM) approach, Demirakca and colleagues studied gray matter (GM) concentrations and volumes of the hippocampus in 11 chronic recreational cannabis users and 13 healthy controls and correlated their findings with THC and CBD measurements made from hair analyses. They found that cannabis users showed lower GM volume in the right anterior hippocampus. Higher THC and lower CBD were associated with this hippocampal volume reduction, suggesting neurotoxic effects of THC and neuroprotective effects of CBD.
The conflicting results among volumetric brain studies seem to result from differences in time span (e.g., age of onset), patterns of cannabis use (e.g., frequency, duration of use, cumulative lifetime use), and type of cannabis used (e.g., potency, CBD/THC ratio) (29, 30).
Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone’s individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Many recreational users of cannabis will never be faced with serious or permanent health deficits. However, for some users, the use of cannabis may cause undesirable psychological side effects, such as cognitive impairment, anxiety and paranoia, and an increased risk of developing chronic psychosis and addiction. Despite all of the publicity surrounding cannabis, remarkably few studies have been performed that examined the relationship between a possibly harmful effect of THC and a possibly protective effect of CBD. The few studies that exist on the effects of CBD show that this cannabinoid can counteract some of the negative effects of THC, although their results have not always been consistent. The question remains how the findings from laboratory studies, often employing high doses of CBD and high CBD/THC ratios, can be extrapolated to the typical practices of the recreational cannabis user. Few or no adverse effects of CBD have been proffered, and where CBD has been found to have an effect, it is usually in a “positive” (i.e., salubrious) direction. The evidence favoring a beneficial effect of CBD therefore merits further investigation in studies in which the amounts and ratios of CBD and THC correspond to the daily practices of recreational cannabis use.