Cannabis use disorder

Pathophysiology - Brain on Bud

• Primary psychoactive agent: Δ⁹-tetrahydrocannabinol (THC).
• Mechanism: THC acts as a partial agonist at cannabinoid receptors (CB1 & CB2).
  • CB1 Receptors (Brain): High density in the hippocampus, cerebellum, basal ganglia, and cortex. Activation inhibits presynaptic neurotransmitter (GABA, glutamate) release, causing psychoactive effects.
  • CB2 Receptors (Periphery): Primarily on immune cells, mediating immunomodulatory effects.
• Reward Pathway: THC ↑ dopamine in the nucleus accumbens, reinforcing use.

⭐ Chronic use causes downregulation and desensitization of CB1 receptors, contributing to tolerance.

Diagnosis (DSM-5) - Spotting the Stoner

• A problematic pattern of cannabis use leading to clinically significant impairment or distress, with ≥2 of the following criteria occurring within a 12-month period.

• Core Domains:

  • Impaired Control: Using more/longer than intended; unsuccessful efforts to cut down; excessive time spent; craving.
  • Social Impairment: Failure to fulfill major role obligations; continued use despite social problems; giving up important activities.
  • Risky Use: Use in hazardous situations; continued use despite physical or psychological problems.
  • Pharmacological: Tolerance; withdrawal.

⭐ Severity Specifiers: Based on the number of criteria met:

• Mild: 2-3 criteria
• Moderate: 4-5 criteria
• Severe: ≥6 criteria

Intoxication & Withdrawal - The Highs and Lows

Intoxication ("High"):

• Psychological: Euphoria, anxiety, paranoia, slowed time perception, impaired judgment.
• Physical: Conjunctival injection (red eyes), ↑ appetite, dry mouth (xerostomia), tachycardia.
• Perceptual: Colors, sounds, and tastes may seem more intense.

Withdrawal:

• Symptoms: Irritability, anxiety, depression, insomnia, restlessness, headaches, ↓ appetite.
• Timeline: Begins within 24-72 hours, peaks in the first week, and can last up to 2 weeks.

⭐ High-Yield: Due to high lipophilicity, THC is stored in fat and can be detected in urine for up to 30 days in chronic users.

Management - Clearing the Haze

• Backbone: Psychosocial interventions are first-line.
  • Cognitive Behavioral Therapy (CBT): Reshape maladaptive thoughts/behaviors.
  • Motivational Interviewing (MI): Bolster intrinsic desire for change.
  • Contingency Management: Tangible rewards for abstinence.
• Withdrawal: Primarily supportive care (reassurance, hydration).
• Pharmacotherapy: Consider for severe symptoms (off-label).
  • Dronabinol (agonist therapy)
  • Gabapentin

⭐ Despite its prevalence, there are currently no FDA-approved medications for the treatment of cannabis use disorder.

Complications - The Aftermath

• Psychiatric: ↑ risk of psychosis (especially in adolescents), anxiety, depression, and amotivational syndrome (apathy, ↓ drive).
• Cannabinoid Hyperemesis Syndrome (CHS): Characterized by cyclical, severe nausea and vomiting, with compulsive hot showering for relief.
• Medical: Chronic bronchitis, potential ↑ risk for MI and stroke.

⭐ Adolescent cannabis use is strongly associated with a 2-4x increased risk of developing schizophrenia in adulthood.

• The primary psychoactive component is delta-9-tetrahydrocannabinol (THC), which acts on cannabinoid receptors CB1 and CB2.
• Intoxication presents with euphoria, anxiety, impaired coordination, conjunctival injection, dry mouth, and increased appetite.
• Withdrawal syndrome manifests as irritability, anxiety, insomnia, and decreased appetite, typically peaking at 48 hours.
• Chronic use is associated with amotivational syndrome and can precipitate psychosis in vulnerable individuals.
• Look for cannabinoid hyperemesis syndrome: episodic, severe vomiting relieved by hot showers.