Self-medication with Cannabis and Nicotine Points to a Potential Alternative to serotonin reuptake inhibitors

Abstract

Over the past five years, there has been an unsettling increase in prevalence rates of depression, with the fastest gains belonging to young adults. To date, no pharmaceutical interventions are sufficient for the treatment of mild to moderate depression. The purpose of this paper was to review the relevant literature and propose a novel therapeutic approach for mild to moderate depression utilizing nicotine and URB597. URB597 is used to increase the concentration of the endocannabinoid anandamide (AEA). AEA and trans-??-tetrahydrocannabinol (THC) are both ligands to the same intercellular receptor called CB1. AEA and THC are the active ingredients of marijuana that have anti-depressant effects. URB597 increases AEA by inhibiting the enzyme fatty acid amide hydrolase (FAAH). Without FAAH, AEA cannot be eliminated, thereby increasing its relative concentration. The CB1 receptor is predominantly found in the basolateral amygdala, the anterior cingulate cortex, the prefrontal cortex, and the hippocampus. These brain regions are highly involved in emotional regulation. The propagation of CB1 receptors in these brain regions is indicative of an endocannabinoid mediated regulatory function. Further evidence supporting the endocannabinoid system’s effect on the emotional regulation of anxiety involves the pharmacological or genetic disruption of the CB1 receptor. Animal studies have shown disrupting the activities of CB1 provokes anxiety-like behavior. In contrast, stimulation by AEA has not only been shown to reduce anxiety, depression, neuropathic pain but positively affects sentiments toward traumatic events. Activation of the endocannabinoid system by increasing AEA concentrations also attenuates the addictive properties of nicotine and positively impacts generalized coping skills. URB597 is nonaddictive, non-toxic, and has no known adverse side effects and is currently under-investigated as a potential therapy for opioid addiction. The combination of URB597 with nicotine has the promise to help millions of people by reducing the impairment produced by this mild to moderate depression.