title: Enhancing Brain Pregnenolone May Protect Cannabis Intoxication but Should Not Be Considered as an Anti-addiction Therapeutic: Hypothesizing Dopaminergic Blockade and Promoting Anti-Reward.
abstract: Many US states now embrace the medical and recreational use of Cannabis. Changes in the laws have heightened interest and encouraged research into both cannabinoid products and the potential harms of Cannabis use, addiction, and intoxication. Some research into those harms will be reviewed here and misgivings about the use of Pregnenolone, to treat cannabis addiction and intoxication explained. Pregnenolone considered the inactive precursor of all steroid hormones, has recently been shown to protect the brain from Cannabis intoxication. The major active ingredient ofCannabis sativa(marijuana), Δ9-tetrahydrocannabinol (THC) enhances Pregnenolone synthesis in the brain via stimulation of the type-1 cannabinoid (CB1) receptor. This steroid has been shown to inhibit the activity of the CB1receptor thereby reducing many of the effects of THC. While this mechanism seems correct, in our opinion, Vallee et al., incorrectly suggest that blocking CB1receptors could open unforeseen approaches to the treatment of cannabis intoxication and addiction. In this hypothesis, we caution the scientific community that, other CB1receptor blockers, such as, Rimonabant (SR141718) have been pulled off the market in Europe. In addition, CB1receptor blockers were rejected by the FDA due to mood changes including suicide ideation. Blocking CB1receptors would result in reduced neuronal release of Dopamine by disinhibition of GABA signaling. Long-term blockade of cannabinoid receptors could occur with raising Pregnenolone brain levels, may induce a hypodopaminergic state, and lead to aberrant substance and non-substance (behavioral) addictions.
authors: Department of Psychiatry & Mcknight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA ; Department of Addiction Research & Therapy, Malibu Beach Recovery Center, Malibu Beach, CA, USA ; Department of Psychiatry, University of Vermont, Burlington, VT, USA ; Department of Clinical Neurology, Path Foundation NY, NY, USA.
authors: Kenneth
authors: K
authors: Blum
authors: Departments of Psychiatry, Neurology, and Anatomy & Neurobiology, Boston University School of Medicine, and Boston VA Healthcare System, Boston, MA, USA.
authors: Marlene
authors: M
authors: Oscar-Berman
authors: Department of Psychiatry & Mcknight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA ; Department of Clinical Neurology, Path Foundation NY, NY, USA.
authors: Eric R
authors: ER
authors: Braverman
authors: Department of Psychiatry & Mcknight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA.
authors: Marcelo
authors: M
authors: Febo
authors: Department of Clinical Neurology, Path Foundation NY, NY, USA.
authors: Mona
authors: M
authors: Li
authors: Director of Research, Drug Enforcement Administration (DEA) Educational Foundation, Washington, D.C, USA ; Departments of Psychiatry & Behavioral Sciences at the Keck, University of Southern California, School of Medicine, Los Angeles, CA, USA.
authors: Mark S
authors: MS
authors: Gold
keywords: CB1 type receptors; Cannabis; Dopamine; Pregnenolone; Reward deficiency syndrome (RDS)