Deaths due to cannabis use are not known. The median lethal dose in rats was 800 to 1,900 mg (depending on strain) oral THC per kilogram body weight. In studies with monkeys no deaths were recorded following the highest applied doses of 9,000 mg/kg oral THC.
All possible side effects are dose dependent. Therapy should start with low doses, slowly increasing, so that the individual dose can be determined and unwanted effects can be avoided.
Known psychic side effects are sedation, euphoria ("high"), dysphoria, fear to die, feeling to loose control, impairment of memory, altered time perception, depression, hallucinations. In case of strong psychic side effects the affected should be brought to a calm place and "talked down". Cognition and psychomotor performance are attenuated. A discrete reduction of psychomotor performance may be observed up to 24 hours after the administration of THC.
Frequent acute physical side effects are dry mouth, movement disorder, muscle weakness, slurred speech, increase of heart rate, decrease of blood pressure in vertical position, eventually with dizziness. In case of dizziness the affected should lay down. In horizontal position a slightly higher blood pressure may be measured. Rare side effects are nausea and head aches.
All acute side effects are dose dependent and generally disappear within hours or 1-3 days without specific treatment.
Development of tolerance is described for a multitude of effects, among them psychic actions, psychomotor impairment, effects on heart and circulation, effects on the hormonal system, intraoccular pressure, and anti-emetic effects. Tolerance means, that the effect decrease with time during use of cannabis. Tolerance may appear with repeated doses within weeks with different extent for different effects.
Cannabis possesses a potential for addiction. Dependency may not be a relevant problem within the bounds of therapy of diseases, but withdrawal may be unwanted. Withdrawal have not been described in patients that were long-term treated with THC. But withdrawal has been observed in recreational users. Thereby psychic symptoms (anxiety, restlessness, insomnia) and physical symptoms (salivation, diarrhoea) may occur.
The course of a psychosis may be influenced unfavourably. In vulnerable persons the onset of a psychosis may be accelerated or triggered.
Cannabinoids may exert complex effects on male and female sex hormones, their clinical relevance in therapeutic doses being low. Occasionally menstrual cycles without ovulation and impairment of sperm production have been described. In animal studies high doses of THC suppress several aspects of the immune system. In low doses immunosuppressing as well as immunostimulating have been ascertained. Cannabis does not accelerate the progression of HIV/AIDS, however, a chronic administration of THC may be unfavourable in otherwise immunocompromised individuals.