Cannabis

What is it?

Cannabis comes from the Cannabis sativa plant and contains multiple active compounds, with THC (tetrahydrocannabinol, responsible for psychoactive effects) and CBD (cannabidiol, without relevant psychoactive effects) being the most important. It is mainly metabolised by the liver enzymes CYP3A4 and CYP2C19, the same ones that process many antiretrovirals.

How is it used?

• Smoked: joints, pipe, or bong
• Vaporised: devices that heat without combustion
• Edibles: cookies, gummies, oils, infusions
• Oils and tinctures: sublingual use or mixed with food

Non-smoked forms reduce the risk of lung harm and may allow more dose control.

How does it work?

THC and CBD act on the endocannabinoid system, a signalling system found throughout the body. By binding to CB1 receptors (mainly in the central nervous system) and CB2 receptors (in the immune system and peripheral tissue), they can produce:

• Changes in sensory perception and time perception
• Muscle relaxation and sedation
• Increased appetite
• Euphoria or a sense of well-being at low doses
• Anxiety, paranoia, or psychosis at high doses or in sensitive people
• Effects on short-term memory

Effects vary a lot depending on the route of administration, THC concentration, individual tolerance, and context.

Interactions with antiretrovirals

Interactions between cannabis and antiretrovirals mainly happen because they share the same liver enzymes (CYP3A4, CYP2C19). Depending on the medicine, cannabis may increase or decrease blood levels of the antiretroviral.

Cannabis may INCREASE levels of some ARVs

Higher antiretroviral levels may cause:

• Liver damage
• More intense nausea and vomiting
• Cardiac arrhythmias
• Greater overall toxicity

Cannabis may DECREASE levels of some ARVs

Lower antiretroviral levels may cause:

• Reduced treatment effectiveness
• Risk of HIV resistance

Medicines that require more caution

Group / Medicine	Interaction risk	Notes
Protease inhibitors (PI): lopinavir/ritonavir, atazanavir, darunavir	High	Shared CYP3A4 pathway; may alter ARV levels in both directions
NNRTIs: efavirenz, etravirine	Moderate-high	Interaction through CYP3A4 and CYP2C19; efavirenz may reduce cannabinoid levels
Integrase inhibitors: elvitegravir, bictegravir	Moderate	Elvitegravir (boosted with cobicistat) has greater interaction potential
Maraviroc	Moderate	Metabolised by CYP3A4; levels may be affected

Current evidence is limited and human studies are scarce. More research is needed, especially with protease and integrase inhibitors.

Harm reduction

• Use the lowest amount possible and as infrequently as possible
• Avoid strains or products with very high THC concentrations
• Prefer non-smoked forms (vaping, edibles, tinctures) to reduce lung harm
• Stay consistent with ART: do not skip doses because of cannabis use
• Tell your healthcare team about cannabis use so they can monitor possible interactions
• Do not combine with alcohol if possible (more sedation and nausea risk)
• Be especially careful if you use protease inhibitors or efavirenz

Warning signs

These may suggest an ART interaction or an adverse reaction:

• Persistent nausea or vomiting that is unusual for you
• Excessive dizziness or drowsiness
• Palpitations or chest pain
• Confusion or severe anxiety that does not improve

When should you seek medical care?

• Chest pain or pressure
• Trouble breathing
• Fainting or loss of consciousness
• Severe confusion or disorientation that does not improve
• Symptoms that worry you or feel unusual

What does the evidence say?

Cannabis and antiretroviral interactions are possible and have been described in a preliminary way, especially with protease inhibitors and some integrase inhibitors. Most available studies are in vitro or small case series. Robust clinical evidence is still limited, but caution is justified, especially with treatments that have narrow therapeutic windows.

Telling your healthcare team allows appropriate monitoring and dose adjustments if needed.