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Cannabis Use Disorder

Cannabis Use Disorder: Clinical findings and Complications Authors: Iqra Rahamatullah Mahrukh Kaimkhani Reviewers: Keira Britto Sara Cho Luiza Radu Alex Kennedy* *MD at time of publication Tetrahydrocannabinol (THC) in cannabis binds human cannabinoid receptor 1 (CB1) receptors in ventral tegmental area Biological factors: earlier age of cannabis use onset, male gender, genetic predisposition Psychosocial factors: stress, aggression, depression, anxiety, parent/peer cannabis or other substance use, ↓ SES, family dysfunction, bullying, occupational difficulties Disinhibits dopaminergic signaling and reward response ↑ Motivation to continue cannabis use Cannabis Use Disorder Cannabis use that may lead to significant distress or impairment in psychological, physical, or social functioning Cannabis (CB1 receptor agonist), especially with ↑ THC, acutely causes burst firing of ventral tegmental area ↑ Dopamine in striatal and prefrontal areas ↑ Dopaminergic transmission in the mesolimbic pathway (neuronal network involved in mediation of psychosis) Delusions, hallucinations, & paranoia occurring with acute or chronic use Cannabis induced psychotic disorder ↑ THC activates CB1 receptors on GABAergic terminals & ↓ THC activates CB1 receptors on glutaminergic terminals GABA & glutamate dysregulation and imbalance (can occur with acute or chronic use) Repeated exposures to ↑THC results in serotonin (5- HT) receptor upregulation ↑ Neuro- endocrine responses of stress hormones, which may ↑ serotonin reuptake Sedative action of low dose THC on CB1 receptors causes ↓ sleep latency and ↑ slow wave sleep with acute cannabis use Tolerance with chronic usage causes reversal of acute effects ↑ Sleep latency & ↓ slow wave sleep ↓ Sleep time & quality; ↓ cerebral restoration & recovery Cannabis induced sleep disorder Chronic cannabinoid receptor overstimulation Receptor dysregulation, desensitization, and downregulation Hypothalamic pituitary adrenal (HPA) axis dysregulation Inhibited gastrointestinal motility and digestion Nausea & vomiting & abdominal pain after cannabis use Cannabinoid hyperemesis syndrome (cyclic vomiting with cannabis use) Down regulation of CB1 receptors due to long term cannabis usage, paired with sudden discontinuation of cannabis use ↓ Cannabinoid in ↑CB1 receptors disrupts emotional processing, sleep and appetite homeostasis within the endocannabinoid system Anxiety, irritability, anger, depression, sleep disruption, appetite loss. Cannabinoid withdrawal Mood changes, anxiety and/or panic attacks Cannabis induced mood and anxiety disorders Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 11, 2024 on www.thecalgaryguide.com Sympathetic nervous system dysregulation