Brain Anatomical Alterations in Young Cannabis Users: Is it All Hype? A Meta-Analysis of Structural Neuroimaging Studies

Lorenzetti, Valentina; Kowalczyk, Magdalena; Duehlmeyer, Leonie; Greenwood, Lisa-Marie; Chye, Yann; Yücel, Murat; Whittle, Sarah; Roberts, Carl A.

doi:10.1089/can.2021.0099

Cited by 10 publications

(5 citation statements)

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“…In fact, previous research reported a weak association between occasional cannabis smoking and impaired reward-based decision-making, and between occasional cannabis smoking and structural brain abnormalities (40,41). Additionally, a recent meta-analysis conducted by Lorenzetti et al (42) did not reveal any GM and WM volume reductions in adolescent cannabis users in comparison to non-cannabis users. In the current study, occasional cannabis use was defined as smoking cannabis two or less times per week.…”

Section: Inclusion and Exclusion Criteriamentioning

confidence: 86%

Chronic tobacco smoking, impaired reward-based decision-making, and role of insular cortex: A comparison between early-onset smokers and late-onset smokers

Conti

Baldacchino

2022

Front. Psychiatry

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IntroductionThe literature suggests that tobacco smoking may have a neurotoxic effect on the developing adolescent brain. Particularly, it may impair the decision-making process of early-onset smokers (<16 years), by rendering them more prone to impulsive and risky choices toward rewards, and therefore more prone to smoking relapses, in comparison to late-onset smokers (≥16 years). However, no study has ever investigated reward-based decision-making and structural brain differences between early-onset smokers and late-onset smokers.MethodsComputerized measures of reward-based decision-making [Cambridge Gambling Task (CGT); 5-trials adjusting delay discounting task (ADT-5)] were administered to 11 early-onset smokers (mean age at regular smoking initiation = 13.2 years), 17 late-onset smokers (mean age at regular smoking initiation = 18.0 years), and 24 non-smoker controls. Voxel-based morphometry (VBM) was utilized to investigate the gray matter (GM) and white matter (WM) volume differences in fronto-cortical and striatal brain regions between early-onset smokers, late-onset smokers, and non-smokers.ResultsEarly-onset smokers displayed a riskier decision-making behavior in comparison to non-smokers as assessed by the CGT (p < 0.01, Cohen’s f = 0.48). However, no significant differences (p > 0.05) in reward-based decision-making were detected between early-onset smokers and late-onset smokers. VBM results revealed early-onset smokers to present lower GM volume in the bilateral anterior insular cortex (AI) in comparison to late-onset smokers and lower WM volume in the right AI in comparison to late-onset smokers.ConclusionImpairments in reward-based decision-making may not be affected by tobacco smoking initiation during early adolescence. Instead, lower GM and WM volume in the AI of early-onset smokers may underline a vulnerability to develop compulsive tobacco seeking and smoking behavior during adulthood.

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Section: Inclusion and Exclusion Criteriamentioning

confidence: 86%

Chronic tobacco smoking, impaired reward-based decision-making, and role of insular cortex: A comparison between early-onset smokers and late-onset smokers

Conti

Baldacchino

2022

Front. Psychiatry

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“…Alternatively, unmeasured variables entrenched with cannabis use may explain the emerging alterations in a portion of the studies. The variables might include: greater cannabis use related problems (Lorenzetti et al, 2016 , 2020 ; Chye et al, 2019 ; Rossetti et al, 2021 ), poly-substance use (e.g., nicotine, alcohol; Brody et al, 2004 ), substance-related psychosocial variables (Jackson et al, 2020 ) and young age (mean = 22 years, range = 16–28 years in the reviewed literature), which may protect from the adverse impact of cannabis use on the brain (Lorenzetti et al, 2023 ). Notably, a paucity of studies measured potential moderators in relation to brain function (e.g., sex; Becker and Chartoff, 2019 ), and more evidence is required to test these notions.…”

Section: Discussionmentioning

confidence: 99%

Brain reward function in people who use cannabis: a systematic review

Beyer,

Poudel,

Antonopoulos

et al. 2024

Front. Behav. Neurosci.

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RationaleCannabis is one of the most widely used psychoactive substances globally. Cannabis use can be associated with alterations of reward processing, including affective flattening, apathy, anhedonia, and lower sensitivity to natural rewards in conjunction with higher sensitivity to cannabis-related rewards. Such alterations have been posited to be driven by changes in underlying brain reward pathways, as per prominent neuroscientific theories of addiction. Functional neuroimaging (fMRI) studies have examined brain reward function in cannabis users via the monetary incentive delay (MID) fMRI task; however, this evidence is yet to be systematically synthesised.ObjectivesWe aimed to systematically integrate the evidence on brain reward function in cannabis users examined by the MID fMRI task; and in relation to metrics of cannabis exposure (e.g., dosage, frequency) and other behavioural variables.MethodWe pre-registered the review in PROSPERO and reported it using PRISMA guidelines. Literature searches were conducted in PsycINFO, PubMed, Medline, CINAHL, and Scopus.ResultsNine studies were included, comprising 534 people with mean ages 16-to-28 years, of which 255 were people who use cannabis daily or almost daily, and 279 were controls. The fMRI literature to date led to largely non-significant group differences. A few studies reported group differences in the ventral striatum while participants anticipated rewards and losses; and in the caudate while participants received neutral outcomes. A few studies examined correlations between brain function and withdrawal, dosage, and age of onset; and reported inconsistent findings.ConclusionsThere is emerging but inconsistent evidence of altered brain reward function in cannabis users examined with the MID fMRI task. Future fMRI studies are required to confirm if the brain reward system is altered in vulnerable cannabis users who experience a Cannabis Use Disorder, as postulated by prominent neuroscientific theories of addiction.

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“…With respect to long-term brain and neurodevelopmental alterations, several systematic reviews were published in 2023 to assess findings across neuroimaging modalities. Specifically, the reviews compiled data across studies using positron emission tomography to assess molecular brain differences (Xu et al, 2023), functional MRI to assess connectivity changes (Soleimani et al, 2023), MRI to assess anatomical and structural alterations (Lorenzetti et al, 2022), and diffusion-weighted MRI to assess white matter microstructure (Robinson et al, 2023). Together, these reviews reported molecular differences in dopamine and not been copyedited and formatted.…”

Section: Ivb1 δ9-thcmentioning

confidence: 99%

The Development of Cannabinoids as Therapeutic Agents in the United States

Murray,

Gannon,

Winsauer

et al. 2024

Pharmacol Rev

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Cannabis is one of the oldest and widely used substances in the world. Cannabinoids within the cannabis plant, known as phytocannabinoids, mediate cannabis' effects through interactions with the body's endogenous cannabinoid system. This endogenous system, the endocannabinoid system, has important roles in physical and mental health. These roles point to the potential to develop cannabinoids as therapeutic agents, while underscoring the risks related to interfering with the endogenous system during non-medical use. This scoping narrative review synthesizes the current evidence for both the therapeutic and adverse effects of the major (i.e., Δ9-tetrahydrocannabinol and cannabidiol) and lesser studied minor phytocannabinoids, from nonclinical to clinical research. We pay particular attention to the areas where evidence is well-established, including analgesic effects after acute exposures, and neurocognitive risks after acute and chronic use. In addition, drug development considerations for cannabinoids as therapeutic agents within the United States are reviewed. The proposed clinical study design considerations encourage methodological standards for greater scientific rigor and reproducibility, ultimately, to extend our knowledge of the risks and benefits of cannabinoids for patients and providers. Significance StatementThis work provides a review of prior research related to phytocannabinoids, including therapeutic potential and known risks in the context of drug development within the United States. We also provide study design considerations for future cannabinoid drug development. IV.A.1. Analgesia IV.A.1.a. Δ9-THC IV.A.1.b. Sex differences in the analgesic effects of Δ9-THC IV.A.1.c. Analgesic effects of CBD and minor cannabinoids IV.A.2. Clinical assessment of other therapeutic outcomes IV.A.2.a. Δ9-THC IV.A.2.b. CBD and other minor cannabinoids IV.B. Evidence for adverse effects IV.B.1. Δ9-THC IV.B 2. CBD and other minor cannabinoids V. Clinical study design considerations V.A. Variability in protocol design V.A.1. Drugs and comparators V.A.2. Route and timing of administration V.A.3. Dose and dosing duration V.A.4. Study design V.A.5. Eligibility criteria and sample size V.B. Variability in outcome assessment V.B.1. Assessment of therapeutic outcomes V.B.1.a. Analgesia V.B.1.b. Other therapeutic outcome measures V.B.2. Assessment of adverse effects V.B.2.a. Neurocognitive effects and psychosis V.B.2.b. Abuse liability V.C. Hazard and Risk Management of Cannabinoids VI. Conclusions not been copyedited and formatted. The final version may differ from this version. Pharmrev Fast Forward.

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Brain Anatomical Alterations in Young Cannabis Users: Is it All Hype? A Meta-Analysis of Structural Neuroimaging Studies

Cited by 10 publications

References 69 publications

Chronic tobacco smoking, impaired reward-based decision-making, and role of insular cortex: A comparison between early-onset smokers and late-onset smokers

Chronic tobacco smoking, impaired reward-based decision-making, and role of insular cortex: A comparison between early-onset smokers and late-onset smokers

Brain reward function in people who use cannabis: a systematic review

The Development of Cannabinoids as Therapeutic Agents in the United States

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