Salvia divinorum

schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, family history of psychotic disorders

Personal or family history of psychotic disorders is an absolute contraindication. Case reports document persistent psychotic episodes following S. divinorum use in individuals with possible pre-existing psychiatric vulnerability (El-Khoury & Sahakian 2015; Dedomenici et al. 2022). One case required three sequential pharmacological treatments before resolution. KOR agonism-mediated disruption of thalamocortical signalling and dopaminergic suppression may trigger psychotic decompensation in vulnerable individuals.

liver disease, hepatic impairment, cirrhosis

Salvinorin A undergoes hepatic metabolism via multiple CYP isoforms (CYP2D6, CYP2E1, CYP1A1, CYP2C18) and UGT2B7 glucuronidation (Teksin et al. 2009, in vitro data). Impaired hepatic function could theoretically reduce clearance and prolong or intensify effects. No published clinical data exist for this population.

pregnancy, breastfeeding

No published safety data exist for S. divinorum or salvinorin A use during pregnancy or breastfeeding. No animal reproductive toxicity studies have been published. This contraindication is precautionary — based on the absence of safety data rather than documented harm.

adolescents, minors

Adolescent use is a relative contraindication. Multiple reviews flag elevated psychiatric risk in adolescents due to developing brain vulnerability to KOR-mediated dopaminergic suppression. The mesolimbic dopamine system undergoes significant maturation during adolescence, and chronic KOR activation could theoretically disrupt this process.

fluoxetine, paroxetine, quinidine, disulfiram, other CYP2D6 inhibitors, other CYP2E1 inhibitors

Concurrent use of drugs that inhibit CYP2D6 (e.g., fluoxetine, paroxetine, quinidine) or CYP2E1 (e.g., disulfiram) could theoretically increase salvinorin A plasma levels and prolong effects. This is based entirely on in vitro metabolic data (Teksin et al. 2009). No clinical pharmacokinetic interaction study has been conducted.

unsupervised use, fall-risk environment, near water, near heights, while driving

At typical smoked doses, S. divinorum produces complete loss of awareness of the physical environment, severe motor control impairment, and spatial disorientation. Users are unable to respond to environmental hazards during peak effects. Unsupervised use or use in environments with fall risk, open water, heights, or traffic creates direct risk of physical injury.