A temporary form of drug-induced psychotic reaction after administration of oral cannabis has occurred in these two cases. Cannabis psychosis is the term proposed in the literature [10]. In 1958, Ames [11] reported in an experimental design with 10 subjects psychological symptoms such as severe anxiety, panic attacks, paranoid delusions and depersonalization. Talbott [12] in 1969 described 12 soldiers in Vietnam who had disorientation and hallucinations after their first use of cannabis. In Germany, 19 cases of toxic psychosis were reported after hashish use [13] and in Calcutta, Chopra [14] described retrospectively 200 patients hospitalized after the ingestion of large dose of cannabis between 1963 and 1968. Other reports in different countries showed similar features after bhang ingestion [3, 15]. It usually results from taking large amount of the drug, generally in food or drink. The symptoms have some similarity with paranoid schizophrenia, which could raise the hypothesis that " symptoms of schizophrenic illness might be caused by an abnormal over-activity of endogenous cannabinoid mechanism in the brain" (Iversen [10] citing Emrich [16]). However because of the poor quality of information on previous cannabis experience, cannabis dose intake, other drug consumption and previous psychiatric comorbidity, some commentators have criticized these case series [12, 17, 18]. Case-control studies have been conducted comparing people with cannabis psychosis with persons suffering from schizophrenia [19–21]. However the results were inconsistent due in part to the small sample size of these studies.
The originality of our two cases is that they were observed in an experimental setting, and therefore adds more evidence for the ability of oral cannabis to produce psychotic symptoms. In both our subjects, the effects appeared 1 hour to 1.5 hours after oral drug intake and lasted for 3 to 4 hours. Dronabinol (synthetic THC) is reported to have an onset of action at approximately 0.5 to 1 hour and peak effects between 2 and 4 hours. Psychoactive effects last 4 to 6 hours but the appetite stimulant effect may continue for 24 hours [22].
The issue of THC dose level is very important in terms of public health. A traditional cigarette of herbal cannabis in the 1960s and 1970s contained 1–3% THC: for a joint made of 750 mg of cannabis plant, the corresponding THC amount was 7 to 20 mg. However, the actual amount of cannabis taken up (i.e. the percent delivery to the respiratory tree) strongly depends on the smoking technique; it has been reported to reach approximately 50% [23]. Modern cigarettes (joint) based on intensive cannabis selection and improvement in plant cultivation contain 6 to 30% THC. Therefore, an average joint would correspond to 75 mg to 225 mg of THC! [22].
Through smoking, a 3.5% marijuana cigarette with about 900 mg plant materials can achieve plasma concentration in the range of 50 to 100 ng/ml. The maximum psychotropic effect or "high" occurs faster after smoking than by the oral route. Smoking is therefore the preferred route of cannabis administration for young users. Psychomotor function is considered to be obviously impaired above 10 ng/ml plasma THC for smoking cannabis. However in our two cases, the oral administration of cannabis produced circulating THC concentrations much lower than 10 ng/ml. We suggest several explanations for these differences. Firstly, the oral administration produces more active metabolite (11-OH-THC), which could more efficiently reach the effect site than THC. Secondly, as suggested by Chaudry [3], consuming oral cannabis may produce more potent, yet unknown psychotomimetic metabolites of THC. Thirdly, the slow absorption kinetics produces sustained plateau levels in the blood, which could influence the body and brain distribution. In a cocaine fatality, Giroud [24] found that THC and OH-THC were in higher concentration in brain than in blood.
Finally, Leweke [25] in a study including 17 healthy volunteers found also one case that suffered a two-hour episode of paranoid psychotic state following the administration of dronabinol with a lower dose than our study. Furthermore D'Souza [26] administrating intravenous THC to 22 healthy subjects in a double blind randomised clinical trial found a range of transient symptoms resembling those seen in endogenous psychosis. At last, it is important to differentiate these transient psychotic states with spontaneous resolution from the type of psychosis that persist beyond the persistence of drug in the brain, therefore probably indicating a worsening of an underlying pathologic problem.
In conclusion, doctors and users should be aware of the increasing availability of oral cannabis in "special" drinks or food as well as in medications under development. While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur. An increased incidence of psychotic episodes might be induced by this new trend and requires attention regarding this phenomenon in a public health perspective.
