What are the effects of cannabis (tetrahydrocannabinol) on the body?

Effects of Cannabis (Tetrahydrocannabinol) on the Body

Cannabis has significant effects on the body including potential therapeutic benefits for chemotherapy-induced nausea and non-cancer pain, but also carries substantial risks including cognitive impairment, cardiovascular effects, respiratory issues, and psychiatric complications.

Pharmacology and Mechanism of Action

• Cannabis contains over 140 pharmacologically active cannabinoids, with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) being the most prominent 1
• THC produces effects through interaction with the endocannabinoid system via:
  • CB1 receptors (present in cerebral cortex, hippocampus, basal ganglia, cerebellum, peripheral nervous system) - responsible for euphoric effects
  • CB2 receptors (primarily on immune system cells) 1
• The pharmacokinetics vary by administration route:
  • Inhaled cannabis: Effects begin within seconds to minutes, peak at 15-30 minutes, last 2-3 hours
  • Oral cannabis: Effects begin after 30-90 minutes, peak at 2-3 hours, last 4-12 hours 1
• THC concentrations have increased dramatically in recent years, from 9% in 2008 to 17% in 2017, with concentrates reaching up to 70% THC 1, 2

Potential Therapeutic Benefits

• May improve chemotherapy-induced nausea and vomiting when standard antiemetics are inadequate
• May help with non-cancer pain
• No evidence supports using cannabis to treat cancer itself 1
• Other potential therapeutic applications under investigation include:
  • Treatment for HIV/AIDS cachexia
  • Multiple sclerosis spasticity
  • Neuropathic pain 1

Adverse Effects

Acute Effects

1. Cognitive Effects:

   • Impaired memory and learning
   • Decreased coordination and performance
   • Confusion and disorientation 1, 3

2. Cardiovascular Effects:

   • Increased heart rate (tachycardia)
   • Elevated blood pressure
   • Orthostatic hypotension
   • Increased risk of myocardial ischemia in at-risk individuals 2
   • Higher risk of stroke in dose-dependent manner 2

3. Psychological Effects:

   • Anxiety and panic attacks
   • Psychotic symptoms
   • Suicidal ideation in vulnerable individuals 3, 4

4. Other Acute Effects:

   • Hyperemesis syndrome (cyclic vomiting)
   • Dry mouth
   • Dizziness 1, 3

Chronic Effects

1. Neurological Effects:

   • Potential negative impact on brain development in adolescents
   • THC-induced activation of CB1 receptors can inhibit neuronal growth and affect synapsis formation 1
   • Changes in hippocampal structure in regions with high CB1 receptor density 1
   • Neurocognitive impairments with long-term use 3

2. Psychiatric Effects:

   • Increased risk of mood disorders
   • Exacerbation of psychotic disorders in vulnerable individuals
   • Cannabis use disorder and withdrawal syndrome 3, 5

3. Respiratory Effects:

   • Chronic respiratory problems from smoking cannabis 1
   • Vaping cannabis presents unique risks including acute lung injury 2

4. Cardiovascular Effects:

   • Increased risk of adverse cardiovascular events including myocardial infarction and stroke with chronic use 2, 5

Special Considerations

Drug Interactions

• Cannabis inhibits cytochrome P450 enzymes (CYP3A4, UGT1A9, UGT2B7, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19)
• High-risk interactions with:
  • Warfarin (very high risk)
  • Buprenorphine and tacrolimus (high risk)
  • May interact with chemotherapeutics, potentially affecting toxicity or efficacy 1
• Cannabis may reduce efficacy of immunotherapies 1

Vulnerable Populations

• Adolescents: Higher risk of negative impacts on brain development and cognitive function 1, 2
• Older adults: Increased risk of confusion and falls 1
• Individuals with history of psychosis: Higher risk of psychotic symptoms 1
• Patients on immunotherapy: May reduce treatment efficacy 1

Clinical Recommendations

1. For patients considering cannabis use:

   • Start with the lowest possible dose and increase slowly
   • Allow sufficient time between doses to gauge effects
   • Be cautious with edibles as onset may be ≥1 hour after ingestion
   • Avoid "stacking" doses to prevent adverse effects 1

2. For patients using cannabis:

   • Avoid driving while feeling effects (typically 5-8 hours after use)
   • Store cannabis products safely away from children and pets
   • Be aware of local and federal laws regarding cannabis use 1
   • Consider oral (edible) administration rather than smoking/vaping for medical use 1

3. For healthcare providers:

   • Screen for cannabis use patterns in patients with cardiovascular risk factors
   • Discuss potential risks and benefits with patients
   • Monitor for drug interactions, particularly with medications metabolized by cytochrome P450 enzymes 1, 2

Common Pitfalls and Caveats

• Edible cannabis products have delayed onset (up to 2 hours), which can lead to overconsumption and more intense effects due to higher blood concentrations of 11-hydroxytetrahydrocannabinol 1
• Administration with high-fat meals significantly increases oral cannabinoid absorption and may exacerbate effects 1
• Cannabis is federally illegal in the United States despite state-level legalization in many areas 1
• Evidence on long-term effects remains limited due to research restrictions 1
• The perception of cannabis as a benign substance contradicts emerging evidence of significant adverse effects 5, 4