In this phase I safety study, the investigators will evaluate the pharmacokinetics, pharmacoequivalence, and drug-drug interaction profile with current antipsychotics of a new tablet pharmaceutical preparation of cannabidiol in healthy volunteers.
Several studies suggest a strong association between schizophrenia and the endocannabinoid system. This system mediates e.g. the pro-psychotic effects of the best-known ingredient of the cannabis plant – delta-tetrahydrocannabinol (Δ9-THC). While the pro-psychotic Δ9-THC is known to abet the onset of schizophrenia, another, non-psychotomimetic plant ingredient – cannabidiol – has recently been shown to exert antipsychotic effects similar to those of one of the most effective modern antipsychotics, amisulpride, but it induced significantly less side effects.
Pregnancy or lactation
Schedule of enrolment, interventions, visits and assessments. Abbreviations: AE: Adverse event. PANSS: Positive and Negative Syndrome Scale (rating scale – symptom severity). CGI: Clinical Global Impression scale (rating scale – global illness severity), Severity (S) and Improvement (I) scores. PSP: Personal and Social Performance Scale (rating scale – level of psychosocial functioning). SWN: Subjective Well-being Scale under Neuroleptic treatment (rating scale – well-being). BACS: Brief Assessment of Cognition in Schizophrenia (neuropsychiatric test battery). UKU: Udvalget for Kliniske Undersøgelser (rating scale – antipsychotic side effects). PSQI: Pittsburgh Sleep Quality Index (rating scale – subjective sleep quality)
ICD-10 diagnosis of schizophrenia (DF20.X), paranoid psychosis (DF22.X), acute/intermittent psychotic disorder (DF23.X), schizoaffective psychosis (DF25.X), other/not specified non-organic psychotic disorder (DF28/DF29), or cannabis induced psychotic disorder (DF12.5)
There is a lack of knowledge on the treatment of patients with dual diagnosis since research so far has focused on patients with psychosis without comorbid substance use disorder.
Broyd SJ, Van Hell HH, Beale C, Yücel M, Solowij N. Acute and chronic effects of cannabinoids on human cognition – a systematic review. Biol Psychiatry. 2016;79(7):557–67. https://doi.org/10.1016/j.biopsych.2015.12.002.
When the participants are enrolled in the project, the treatment and monitoring will be carried out in collaboration with the psychiatric hospital or outpatient clinic taking care of the patient before and after participation in the trial. If the participant is not enrolled in an outpatient clinic by the time of inclusion, the project staff will refer the patient to an outpatient clinic upon completion of the trial.
This is the first study to investigate a potential new paradigm in the treatment of patients with psychosis and comorbid cannabis use. Patients with dual diagnosis are particularly difficult to treat and are generally afflicted by worse outcomes than patients with psychosis alone. The increasing potency of available cannabis is of global concern [44, 45], and the results of this trial will become increasingly important.
Secondary outcome measures
Protocol version 4.0 04-12-2020.
Insufficient effect of treatment on psychotic symptoms with a need of switching to another antipsychotic compound