Delta-8-THC produced tolerance, dependence, and abuse-like effects similar to delta-9-THC in mice | Research

The takeaway

A controlled study in mice found delta-8-THC produces tolerance, physical dependence, and discriminative stimulus effects qualitatively similar to delta-9-THC, challenging marketing claims that it is a milder alternative.

Delta-8-THC consumers, regulators, and researchers studying cannabinoid pharmacology.

Delta-8 produced delta-9-like dependence and abuse liability in both sexes

What the researchers found

Delta-8-THC produced cannabimimetic effects (catalepsy, antinociception, hypothermia, immobility) at doses above 12.5 mg/kg, all blocked by the CB1 antagonist rimonabant. Repeated administration produced tolerance and cross-tolerance to WIN 55,212-2. Rimonabant-precipitated withdrawal produced physical dependence signs. Delta-8-THC produced delta-9-THC-like discriminative stimulus effects in both sexes.

Why it matters

Delta-8-THC is marketed as a legal, milder alternative to delta-9-THC. This study provides direct evidence that it produces the same types of tolerance, dependence, and abuse liability, undercutting those marketing claims.

The numbers in context

Delta-8-THC active at doses above 12.5 mg/kg. Repeated 50 mg/kg produced tolerance and cross-tolerance. Withdrawal signs observed after 10 mg/kg BID for 6 days. Both male and female mice showed delta-9-THC-like discriminative effects.

How the study worked

Adult male and female C57BL/6J mice were tested in the tetrad battery (catalepsy, antinociception, hypothermia, immobility) after acute delta-8-THC. Tolerance assessed after repeated dosing. Physical dependence assessed via rimonabant-precipitated withdrawal. Drug discrimination tested for abuse potential.

What this study cannot tell us

Animal study, so doses and effects may not directly translate to humans. The doses required for effects were higher than for delta-9-THC, consistent with lower potency. Does not address the full range of subjective human experiences.

How to read the evidence

Moderate: rigorous pharmacological methods in both sexes, but animal study only.

When this study was published

Published in 2022.

The bigger picture

The delta-8-THC market has exploded due to legal loopholes. This is one of the first rigorous studies to assess its dependence and abuse potential, providing evidence that regulators and consumers should take seriously.

Questions still open

Is delta-8-THC truly less potent than delta-9 in humans, or just in mice? Should delta-8-THC be subject to the same regulations as delta-9? Do the tolerance and dependence findings apply to the lower doses typically consumed by humans?

Common questions

Is delta-8-THC really milder than delta-9?

It required higher doses to produce effects in mice, suggesting lower potency. However, it produced the same types of tolerance, physical dependence, and abuse liability, meaning "milder" may be misleading.

Can you become dependent on delta-8-THC?

In mice, yes. Repeated delta-8-THC administration produced physical dependence, with withdrawal signs emerging when a CB1 receptor blocker was given.

Why is delta-8 legally available?

Delta-8-THC can be derived from hemp-sourced CBD, which some interpret as making it legal under the 2018 Farm Bill. However, its pharmacological similarity to delta-9-THC raises regulatory questions.

Read the original research

Assessment of dependence potential and abuse liability of Δ8-tetrahydrocannabinol in mice.

Drug and alcohol dependence, 240, 109640

View on PubMed ↗Publisher’s paper ↗

Citation

Vanegas, S O; Reck, A M; Rodriguez, C E; Marusich, J A; Yassin, O; Sotzing, G; Wiley, J L; Kinsey, S G. (2022). Assessment of dependence potential and abuse liability of Δ8-tetrahydrocannabinol in mice.. Drug and alcohol dependence, 240, 109640. https://doi.org/10.1016/j.drugalcdep.2022.109640