A Historical Cannabis Review Distinguished Tolerance to Side Effects From Tolerance to Treatment Targets
A 1981 review emphasized that tolerance can have different clinical implications depending on which effect becomes weaker. Reduced adverse effects and reduced response on a treatment target should not be described as the same therapeutic development.
Tolerance needs an identified endpoint
The source discussed cardiovascular, autonomic, sleep and behavioral adaptation, with dose and administration schedule affecting its acquisition. A general statement that someone is tolerant leaves unanswered which response changed and under what exposure history.
Adaptation can have different practical meanings
A reduction in an unwanted effect may improve tolerability, while a reduction in a desired effect may undermine the original treatment goal. The distinction is conceptual; the review does not establish a modern dosing strategy for epilepsy, pain or any other condition it discussed.
Dependence is a separate inference
The review described withdrawal observations and distinguished their clinical significance from drug-seeking behavior, which has multiple determinants. Withdrawal, tolerance and a use-disorder diagnosis should not be substituted for one another. Its historical characterization of withdrawal severity should not be treated as a universal current estimate.
Interpreting the evidence
For a clinical tolerance claim, specify whether the endpoint is an adverse reaction, desired benefit or another response. This review supplies an interpretive distinction rather than evidence that adaptation necessarily improves treatment or that a tolerant person is free of functional effects.
Related reading: interpreting cannabis tolerance claims.
Research reference
Jones RT; Benowitz NL; Herning RI (1981). Clinical relevance of cannabis tolerance and dependence. Journal of clinical pharmacology. doi:10.1002/j.1552-4604.1981.tb02589.x.
This analysis draws on the supplied abstract of a historical review.
