Inconsistency in the Composition of the Smoke of a Cannabis Cigarette as Smoking Progresses: Results, Mechanism, and Implications.

Background: The efficacy of cannabis treatment is determined by the active pharmaceutical ingredients (APIs) of the ingested composition. Despite smoking predominancy in cannabis treatment, very little is known regarding its yield and provision rate of cannabis APIs. Material and Methods: Ten experiments were performed, studying changes in APIs content during smoking, using a designated smoking machine. APIs content was evaluated via analysis of a cigarette's residuals and of the smoke composition; cannabinoid and terpene content were assessed. Results: Results demonstrated increased cannabinoid content in the cigarette sections closer to the mouth, as compared with those closer to the lit end. Similarly, cannabinoid content in the inhaled smoke increases as smoking progresses. Similar results are found for sesquiterpenes. Monoterpenes, having lower boiling points reach the smoke before the sesquiterpenes and cannabinoids do. Conclusion: A mechanism is proposed, including: (i) decarboxylation and evaporation of APIs adjacent to the lit end, (ii) transition of API vapors away from the hot zone, (iii) condensation of APIs in cigarette's sections closer to the mouth, and (iv) re-evaporation of APIs as the hot zone approaches, thereby reaching the smoke. Differences in the boiling points between the various APIs result in varying composition along the cigarette and in the inhaled smoke. The main implications are: (i) APIs delivery through smoking cannot be uniform, (ii) APIs amount per puff increases as smoking progresses, and (iii) terpenes are inhaled before the cannabinoids are. Thus, in addition to its known health-threatening hazards, smoking entails nonuniform provision of APIs, even within the same cigarette.