Hippocampal harms, protection and recovery following regular cannabis use.
Murat Yücel, Valentina Lorenzetti, Chao Suo, Andrew Zalesky, Alex Fornito, Michael Takagi, Dan I Lubman, Nadia Solowij
Translational Psychiatry January 12, 2016 DOI: 10.1038/tp.2015.201 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cross-sectional study with subgroup comparisons Peer reviewed |
|---|---|
| Sample size | 111 |
| Population | 74 long-term regular cannabis users (average 15.4 years of use), including THC-only users, THC plus CBD users, and former users with sustained abstinence, plus 37 non-user healthy controls |
| Measures | hippocampal volume, fractional anisotropy, N-acetylaspartate (NAA) |
| Topics | Cannabis |
| Key findings | Cannabis users not exposed to CBD had roughly 11% smaller hippocampal volumes and 15% lower NAA concentrations than controls, whereas users exposed to CBD and former users did not differ from controls on any measure. The authors conclude that ongoing cannabis use is associated with harms to brain health driven by chronic THC exposure, but that these harms appear minimized by CBD and recoverable with extended abstinence. |
Abstract
Shifting policies towards legalisation of cannabis for therapeutic and recreational use raise significant ethical issues for health-care providers seeking evidence-based recommendations. We investigated whether heavy cannabis use is associated with persistent harms to the hippocampus, if exposure to cannabidiol offers protection, and whether recovery occurs with abstinence. To do this, we assessed 111 participants: 74 long-term regular cannabis users (with an average of 15.4 years of use) and 37 non-user healthy controls. Cannabis users included subgroups of participants who were either exposed to Δ9-tetrahydrocannabinol (THC) but not to cannabidiol (CBD) or exposed to both, and former users with sustained abstinence. Participants underwent magnetic resonance imaging from which three measures of hippocampal integrity were assessed: (i) volume; (ii) fractional anisotropy; and (iii) N-acetylaspartate (NAA). Three curve-fitting models across the entire sample were tested for each measure to examine whether cannabis-related hippocampal harms are persistent, can be minimised (protected) by exposure to CBD or recovered through long-term abstinence. These analyses supported a protection and recovery model for hippocampal volume (P=0.003) and NAA (P=0.001). Further pairwise analyses showed that cannabis users had smaller hippocampal volumes relative to controls. Users not exposed to CBD had 11% reduced volumes and 15% lower NAA concentrations. Users exposed to CBD and former users did not differ from controls on any measure. Ongoing cannabis use is associated with harms to brain health, underpinned by chronic exposure to THC. However, such harms are minimised by CBD, and can be recovered with extended periods of abstinence.
Comparable studies
Other cross-sectional and survey studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabis use before age 15 and subsequent executive functioning 104 chronic cannabis users (49 early-onset before age 15, 55 late-onset after age 15)... | 2011 | Observational cross-sectional study | n = 148 |
| Patterns of simultaneous polysubstance use in drug using university students Drug-using university students | 2006 | Cross-sectional survey | n = 149 |
| Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey Online survey respondents | 2020 | Cross-sectional survey | |
| User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study Users of hallucinogenic drugs who completed a web-based questionnaire | 2010 | Cross-sectional survey | n = 600 |
| Illicit Use of LSD or Psilocybin, but not MDMA or Nonpsychedelic Drugs, is Associated with Mystical Experiences in a Dose-Dependent Manner Adults recruited from the MAPS website and newsletter, most reporting use of various... | 2012 | Cross-sectional survey | n = 337 |
Citations in the library
Cited by 22
- Traditional marijuana, high‐potency cannabis and synthetic cannabinoids: increasing risk for psychosis World Psychiatry September 22, 2016
- The neuropsychopharmacology of cannabis: A review of human imaging studies Pharmacology & Therapeutics October 20, 2018
- Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Journal of Psychopharmacology April 23, 2019
- Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like effects? Psychological Medicine September 4, 2018
- Not Just a Pot: Visual Episodic Memory in Cannabis Users and Polydrug Cannabis Users: ROC and ERP Preliminary Investigation Frontiers in Human Neuroscience June 11, 2021
and 17 more in the library
Cites 11
- Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Current Pharmaceutical Design September 12, 2012
- Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Archives of General Psychiatry April 1, 2009
- Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol The International Journal of Neuropsychopharmacology September 24, 2009
- Cannabis use and neurocognitive functioning in a non-clinical sample of users Addictive Behaviors February 6, 2014
- The association between regular cannabis exposure and alterations of human brain morphology: an updated review of the literature. Current Pharmaceutical Design 2014
and 6 more in the library