THC
Tetrahydrocannabinol (Δ9-THC)
Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound in cannabis. It is responsible for the characteristic "high" and has the strongest evidence base for pain, nausea, and appetite stimulation among all cannabinoids.
Primary psychoactive cannabinoid. Effects include euphoria, altered perception, impaired short-term memory, and increased appetite.
Quick Facts
- Molecular Formula
- C₂₁H₃₀O₂
- Molecular Weight
- 314.46 g/mol
- Boiling Point
- 157°C (315°F)
- Legal Status (U.S.)
- Schedule I federally in the U
- Research Status
- Extensively researched
About THC
THC was first isolated and synthesized by Raphael Mechoulam and Yechiel Gaoni at the Weizmann Institute in 1964 — one of the foundational discoveries in cannabinoid science. It is produced in the cannabis plant as THCA (tetrahydrocannabinolic acid) and converted to THC through decarboxylation.
THC is a partial agonist at both CB1 and CB2 receptors. Its psychoactive effects are mediated primarily through CB1 receptor activation in the brain — particularly in the prefrontal cortex, hippocampus, basal ganglia, and cerebellum. This explains its effects on mood, memory, motor coordination, and appetite.
The strongest clinical evidence for THC is in chemotherapy-induced nausea and vomiting (CINV), where dronabinol (synthetic THC) and nabilone (synthetic THC analog) have been FDA-approved since the 1980s. For pain, a 2018 Cochrane review of 47 RCTs found moderate-quality evidence for cannabis-based medicines in chronic neuropathic pain.
THC's risk profile is more complex than CBD's. Acute adverse effects include anxiety, paranoia, tachycardia, and impaired cognition. Chronic heavy use is associated with cannabis use disorder (CUD) in approximately 9% of users (rising to ~17% for daily users), and adolescent use is associated with increased risk of psychosis in genetically predisposed individuals.
The therapeutic window for THC is narrow — doses that provide analgesia often also produce psychoactive effects. This is why THC:CBD combination products (like nabiximols/Sativex) are often preferred clinically, as CBD attenuates THC's psychoactivity.
Receptor Affinity
- CB1 partial agonist (high affinity)
- CB2 partial agonist
- GPR18 agonist
- GPR55 agonist
- TRPV2 agonist
Key Mechanisms
- CB1 partial agonism in CNS — psychoactive effects, analgesia, appetite stimulation
- CB2 partial agonism in immune tissue — anti-inflammatory effects
- Inhibits adenylyl cyclase via Gi/o protein coupling
- Modulates dopamine release in mesolimbic pathway — reward and addiction potential
- Inhibits glutamate and GABA release via presynaptic CB1 activation
- TRPV1 activation at high concentrations — analgesic contribution
Clinical Uses & Evidence
Graded using a modified GRADE framework. Grade A = strong evidence; B = moderate; C = preliminary.
Chemotherapy-Induced Nausea & Vomiting
Grade AFDA-approved (dronabinol, nabilone). Multiple RCTs confirm efficacy. Used as second-line when standard antiemetics fail.
Key study: Cochrane Review 2015
HIV/AIDS-Related Anorexia
Grade AFDA-approved (dronabinol). Significant appetite stimulation and weight maintenance in RCTs.
Key study: Beal et al., JAMA 1995
Chronic Neuropathic Pain
Grade BCochrane review of 47 RCTs found moderate evidence for cannabis-based medicines. THC:CBD combinations (nabiximols) most studied.
Key study: Aviram & Samuelly, J Pain Res 2017
Multiple Sclerosis Spasticity
Grade BNabiximols (THC:CBD 1:1) approved in 30+ countries for MS spasticity. Significant reduction in patient-reported spasticity scores.
Key study: Collin et al., Eur J Neurol 2010
Cancer Pain
Grade BSeveral RCTs show benefit for cancer-related pain, particularly neuropathic components. Often used adjunctively with opioids.
Key study: Johnson et al., J Pain Symptom Manage 2010
PTSD
Grade CObservational data and small trials suggest symptom reduction, particularly nightmares. Larger RCTs needed. Risk of CUD in this population warrants caution.
Key study: Jetly et al., Psychoneuroendocrinology 2015
Side Effects
Drug Interactions
Additive CNS depression; may allow opioid dose reduction (opioid-sparing effect)
May antagonize antipsychotic effects; increased psychosis risk in schizophrenia
CYP2C9 inhibition may increase anticoagulant levels
Additive CNS depression; significantly impairs driving
Additive cardiovascular stress; increased tachycardia and hypertension
CBD attenuates THC psychoactivity via CB1 negative allosteric modulation
Always consult a pharmacist or physician before combining cannabis with prescription medications. This list is not exhaustive.
Dosing Notes
Pharmaceutical THC (dronabinol): 2.5–20 mg/day for CINV; 2.5 mg BID for anorexia. Nabiximols (Sativex): 1–12 sprays/day for MS spasticity. For inhaled cannabis, onset is 5–10 min, peak 30 min, duration 2–3 hours. For oral, onset 30–90 min, peak 2–4 hours, duration 4–8 hours. Start low, go slow — especially for opioid-naive patients.
Dosing information is for educational purposes only. Consult a licensed healthcare provider for personalized guidance.
Legal Status
Schedule I federally in the U.S. (rescheduling to Schedule III pending). Legal for adult use in 24 states; medical use in 38 states. Pharmaceutical THC (dronabinol) is Schedule III; nabilone is Schedule II.
Key Sources
- Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA, 2015.
- Medical cannabis for chronic neuropathic pain. Cochrane Database of Systematic Reviews, 2018.
- Cannabis and cannabinoids for the treatment of people with chronic nondancer pain. Cochrane Database, 2018.
- Adverse health effects of non-medical cannabis use. The Lancet, 2009.