The effects of cannabis, such as the feelings of relaxation and the enhanced perception of auditory and visual information is almost exclusively contributed to the effect on the cannabinoid receptors found in the brain. The cannabinoid neurotransmitter, anandamide (N-arachidonoylethanolamide) is an endogenous molecule that binds to the cannabinoid receptors in the brain and can help regulate an individual's appetite, mood, cognition and emotions (The brain from top to bottom, n.d.). Because delta-9 tetrahydrocannabinol and anandamide have similar chemical structures, cannabis can interfere with the processes that anandamide helps to regulate by binding to the cannabinoid receptors (The brain from top to bottom, n.d.)


THC starts by binding to the CB1 receptors for anandamide. Once this has taken place, the activity of multiple enzymes begins to change, such as the activity of cyclic adenosine monophosphate, or cAMP, which is an important enzyme in many biological processes (The brain from top to bottom, n.d.). THC tends to reduce the activity of cAMP, which, in turn produces less protein kinase A (PKA). When PKA is reduced, the potassium and calcium channels in the cells are altered, which can reduce the release of neurotransmitters. Overall, the excitability of the brain's neural network is reduced (The brain from top to bottom, n.d.). On the other hand, the reward circuit is affected with an increase in the release of dopamine. Dopamine has been found in higher quantities in people who are more extraverted and outgoing (comfortable in social situations). It is possible that the increase in the amount of dopamine released when THC is introduced to the brain can help individuals who experience social anxiety to feel more comfortable and less anxious when they are faced with a social situation (The brain from top to bottom, n.d.).

Marco et al. (2011) reviewed evidence implicating CB1 receptors as important in regulating emotional states. CB1 receptors are found in numerous brain regions relevant to emotional control and stress response including the prefrontal cortex, hippocampus, amygdala, and PTSD_stress_brain.gifhypothalamus. Studies that have artificially blocked the CB1 receptors (i.e. in mutant mice) have shown that their subjects demonstrated heightened anxiety relative to controls. Moreover, when a cannabinoid antagonist, rimonabant, was applied to mice, they showed increased levels of anxiety, especially when they were in aversive contexts. In addition, mutant mice lacking CB1 receptors appeared to not benefit from the anti-anxiety actions of benzodiazepines, and further evidence suggested that CB1 receptors have a pertinent role in GABAergic neurotransmission, which directly applies to the mechanisms underlying benzodiazepine effects (Marco et al., 2011). CB1 receptors have been linked with learning and memory processes, particularly the ability to adapt (i.e. extinguish) aversive memories. For instance, evidence suggested that when functioning of CB1 receptors was altered, the ability to extinguish fear conditioning disappeared. Therefore, it has been speculated that the endocannabinoid system may ameliorate heightened fear reactions, and this may relate to the dysfunctional memory processing and disrupted adaptation to new contexts that underlies disorders like PTSD (Marco et al., 2011).

There is evidence that suggests cannabis activates the hypothalamic-pituitary-adrenal (HPA) axis (a major part of the neuroendocrine system that controls reactions to stress and regulates many body processes, including digestion, the immune system, mood and emotions, sexuality, and energy storage) (Hyman & Sinha, 2009). Brain imaging has shown that chronic users have alterations in cortico-limbic circuits that are involved in stress and reward regulation (Hyman & Sinha, 2009). Weidenfeld, Feldman, and Machoulam dopamine.jpg(1994) conducted a study and found that chronic cannabis exposure increased dose-dependent secretion of the stress hormones corticosterone and ACTH. Acute administration of cannabis is also known to increase dopamine transmission in the nucleus accumbens and the mesolimbic reward systems via action on the central cannabinoid receptors (Hyman & Sinha, 2009). This research indicates that in addition to being a response to stress, chronic cannabis consumption may impact brain development and sensitize individuals to the effects of future life stressors (Hyman & Sinha, 2009). Stress then causes a vicious cycle by contributing as a risk factor to increase cannabis use which would in turn alter the brain’s stress and reward systems that enhance stress response, decreases capacity to cope with stress, and increases the salience of the drug and drug use behaviour (Hyman & Sinha, 2009).