How Does Cannabis Affect Brain Health?

Post by Baldomero B. Ramirez Cantu

What are cannabinoids?

Cannabinoids are a broad class of biological compounds found primarily in the cannabis plant. They are known for their interaction with the endogenous cannabinoid system in the human body and have various physiological and psychoactive effects. The two most well-known, used and understood classes of cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD) (Atakan et al., 2012).

Cannabinoids affect the human body and brain by interacting with endogenous cannabinoid receptors. These receptors are highly expressed in brain regions that control cognitive functions, including the neocortex, hippocampus, basal ganglia, and cerebellum (Marsicano and Kuner, 2008). Thus, endogenous cannabinoid signaling can contribute to crucial brain functions like memory, motivation, and motor coordination.

What are cannabinoids used for?

Cannabinoids are used for both clinical and recreational purposes. In clinical settings, cannabinoids are used to manage pain, alleviate chemotherapy-induced nausea, and treat epilepsy (Allan et al., 2018). Recreational use primarily involves the consumption or inhalation of cannabis. Notably, cannabinoids, particularly THC, can induce sensations of euphoria, heighten pleasure response, and stimulate increased appetite (Mahler et al., 2007).

Cannabis use has also shown promise as a therapeutic option in both HIV treatment and opioid use management. In HIV treatment, some studies suggest that cannabis may help alleviate symptoms associated with the virus, such as pain, nausea, and loss of appetite (Ellis et al., 2021). Additionally, it may have potential anti-inflammatory and neuroprotective properties that could benefit those with HIV-related neurological complications. In the context of opioid withdrawal, cannabis may assist individuals in managing withdrawal symptoms and reducing opioid cravings (Lucas et al., 2021).

How do cannabinoids affect brain health?

Cannabis use has notable effects on brain function in the short term and over prolonged periods. In the short term, immediate cognitive impairment is a common consequence, affecting memory, attention, and problem-solving abilities. These effects are typically temporary and subside as the drug is metabolized. Users may also experience altered sensory perception, impacting their perception of time, colors, and sounds. Some users encounter heightened anxiety or paranoia, particularly when consuming high doses or strains with high levels of THC (Wainberg et al., 2021).

In the long term, chronic and heavy cannabis use can have profound implications for brain health. Persistent use, particularly during adolescence when the brain is still developing, may lead to cognitive impairments, including memory deficits, and reduced attention span (Crean et al., 2011). Additionally, there is evidence of an increased risk of mental health issues, such as anxiety disorders and depression (Jefsen et al., 2023). These long-term effects underscore the importance of responsible cannabis use and consideration of individual susceptibility, as the impact on brain health can vary depending on factors like usage patterns, potency, and personal vulnerabilities.

Our understanding of the precise mechanisms by which cannabis affects brain health remains incomplete. We do know that cannabis use can influence sleep patterns, a fundamental contributor to mental and brain well-being. The impact of cannabis on sleep is multifaceted and can be influenced by factors such as the specific cannabinoids present, the method of consumption, the dosage, and individual variations in drug response (Kaul et al., 2021). In some cases, cannabinoids have been reported to have a positive influence on sleep. Many users claim that it helps them fall asleep more easily and can improve the overall quality of their sleep. However, it's important to note that the relationship between cannabis use and sleep is complex, and the effects can be highly variable. While some people experience improved sleep, others may encounter negative effects. For instance, cannabis use can disrupt the sleep cycle by reducing the amount of rapid eye movement (REM) sleep, which is associated with dreams and overall sleep quality (Vaillancourt et al., 2022). 

The takeaway 

The relationship between cannabis use and brain health is complex and multifaceted. Cannabis can have both short- and long-term effects on cognitive function and mental well-being, but these effects can vary significantly among individuals and depend on factors such as frequency of use, potency, and age of use initiation. It is essential for individuals to be well-informed about the potential risks associated with cannabis use, particularly heavy and prolonged use, which may be linked to cognitive impairments and mental health issues, especially when use begins before the brain is fully developed (typically the mid-to-late twenties). Responsible and moderate use, as well as considering individual vulnerability, remains key in minimizing potential harm. Further research is also needed to uncover the full potential of cannabis in clinical settings to mitigate or improve certain conditions or disease symptoms.

References +

Atakan Z. (2012). Cannabis, a complex plant: different compounds and different effects on individuals. Therapeutic advances in psychopharmacology, 2(6), 241–254.

Marsicano, G., and Kuner, R. (2008). Anatomical distribution of receptors, ligands and enzymes in the brain and in the spinal cord: circuitries and neurochemistry. Cannabinoids and The Brain, ed. A. Köfalvi, 161–201.

Allan, G. M., Finley, C. R., Ton, J., Perry, D., Ramji, J., Crawford, K., Lindblad, A. J., Korownyk, C., & Kolber, M. R. (2018). Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms. Canadian family physician Medecin de famille canadien, 64(2), e78–e94.

Mahler, S. V., Smith, K. S., & Berridge, K. C. (2007). Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances 'liking' of a sweet reward. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 32(11), 2267–2278.

Ellis, R. J., Wilson, N., & Peterson, S. (2021). Cannabis and Inflammation in HIV: A Review of Human and Animal Studies. Viruses, 13(8), 1521

Lucas, P., Boyd, S., Milloy, M. J., & Walsh, Z. (2021). Cannabis Significantly Reduces the Use of Prescription Opioids and Improves Quality of Life in Authorized Patients: Results of a Large Prospective Study. Pain medicine (Malden, Mass.), 22(3), 727–739.

Wainberg, M., Jacobs, G. R., di Forti, M., & Tripathy, S. J. (2021). Cannabis, schizophrenia genetic risk, and psychotic experiences: a cross-sectional study of 109,308 participants from the UK Biobank. Translational psychiatry, 11(1), 211.

Crean, R. D., Crane, N. A., & Mason, B. J. (2011). An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. Journal of addiction medicine, 5(1), 1–8.

Jefsen, O. H., Erlangsen, A., Nordentoft, M., & Hjorthøj, C. (2023). Cannabis Use Disorder and Subsequent Risk of Psychotic and Nonpsychotic Unipolar Depression and Bipolar Disorder. JAMA psychiatry, 80(8), 803–810.

Kaul, M., Zee, P. C., & Sahni, A. S. (2021). Effects of Cannabinoids on Sleep and their Therapeutic Potential for Sleep Disorders. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 18(1), 217–227.

Vaillancourt, R., Gallagher, S., Cameron, J. D., & Dhalla, R. (2022). Cannabis use in patients with insomnia and sleep disorders: Retrospective chart review. Canadian pharmacists journal : CPJ = Revue des pharmaciens du Canada : RPC, 155(3), 175–180.

Predicting How Adversity Changes the Brain

Post by Christopher Chen

The takeaway

Environmental stressors alter our brains. These alterations endure over time, and individual deviations from shared neural patterns associated with adversity hold the potential to predict future psychopathology, like anxiety. 

What's the science?

Brain imaging technologies like functional magnetic resonance imaging (fMRI) have enabled researchers to gather evidence that adversity, particularly during early childhood and adolescence, can lead to abnormal brain development. This may play a significant role in later psychological disorders in adulthood. For instance, brain imaging studies have demonstrated that factors like childhood trauma and poverty can impact the volume of crucial brain regions such as the hippocampus and amygdala - brain regions that are integral to emotion and cognitive function.

Specific types of adversity are thought to uniquely affect particular brain regions, however, it’s still unclear how we can predict outcomes from different types of adversity for unique individuals. Recently in Nature Neuroscience, Holz and colleagues leveraged machine learning and brain imaging data to uncover how distinct types of adversity influence the brain, how this varies across individuals, and how we can predict an individual's likelihood of developing anxiety.

How did they do it?

The researchers conducted a comparative analysis of brain images from 169 at-risk individuals and healthy controls who were part of the Mannheim Study of Children at Risk (MARS), a well-known longitudinal investigation tracking these individuals from birth into adulthood. A replication sample was derived from another imaging study known as the IMAGEN study and shared similar demographic characteristics with the MARS group. The researchers used machine learning to develop a normative model of brain development based on adversity in the MARS group. The same model was employed to generate normative brain images for the same at-risk individuals eight years later and for the replication sample from the IMAGEN study. 

The researchers then engaged in a detailed comparison of essential components within and between these three normative brain models. This included employing a measurement called the dice coefficient to assess the extent of overlap between the neural patterns associated with different types of adversity. Additionally, they harnessed individual-specific z-scores (i.e. how many standard deviations a value is from the mean) to gauge the deviation between an individual’s brain images and the normative brain model. By using linear mixed models, they could gauge how these neural deviations at the individual level predicted the manifestation of anxiety.  

What did they find?

In terms of the brain images from at-risk individuals, the researchers observed a consistent neural signature across subjects, implying that heightened adversity impacts similar brain regions. Remarkably, while brain regions like the hippocampus and amygdala, known to be affected by adversity, exhibited changes in volume, the researchers also noted persistent volume changes in non-limbic system regions like the occipital gyrus and thalamus. They further uncovered that this neural signature remained stable over time. 

Using dice coefficients, the researchers showcased the links between specific types of adversity and corresponding changes in distinct brain regions. Adversities such as prenatal maternal smoking and obstetric challenges demonstrated lower dice coefficients, signifying their unique impact on specific brain areas. For instance, prenatal maternal smoking was closely tied to volume expansions in the hippocampus and volume contractions (i.e. reductions) in the postcentral and occipital gyrus. Meanwhile, obstetric adversity correlated with volume expansions in the ventromedial prefrontal cortex (vmPFC) and volume contractions in the anterior cingulate cortex (ACC). 

Perhaps the most intriguing revelation was the predictive capacity of the normative model. The researchers discovered that significant negative deviations (indicating volume reduction) in an individual's brain were associated with a higher predisposition to future anxiety.

What's the impact?

These findings underscore the positive correlation between adversity-induced brain changes and the likelihood of anxiety. Moreover, the research suggests that the effects of adversity on the brain could be more profound and enduring than previously believed. Although the study's scope was limited to adults and a relatively small cohort, its specificity holds promise for aiding researchers and healthcare professionals in developing more targeted and effective strategies to help individuals navigate the repercussions of adversity in their lives.

The Potential of Brain Stimulation During Sleep to Enhance Memory Function

Post by Meredith McCarty

The importance of sleep

Sleep is essential for humans and all living species. Despite being a period of apparent vulnerability during daily life, the maintenance of sleep throughout evolution suggests that sleep is fundamental for neural and bodily function. Sleep deprivation can lead to numerous deficits including altered attention, memory, and learning (Krause et al., 2017).  

While humans spend about a third of their lifetimes asleep, the duration and nature of our sleep differ from that of our nearest primate relatives. Humans spend less time asleep than other primates, and relatively more time is spent in rapid eye movement relative to non-REM sleep (Nunn & Samson, 2018). There are many interesting theories as to the evolutionary origin of such changes in sleep quality and duration (see Nunn et al., 2016 for review), and increasing evidence for the essential role of sleep in memory consolidation. 

Memory consolidation during sleep

Memory consolidation describes the process by which information learned from the environment is transferred from temporary short-term memory into more distributed and permanent long-term memory. There is growing evidence that slow-wave sleep (SWS), a period of non-REM sleep marked by low-frequency, high-amplitude brain waves, is pivotal for memory consolidation (Klinzing et al., 2019).  

During SWS, cortical and subcortical regions, namely the hippocampus, thalamus, and neocortex, exhibit distinct patterns of neural oscillations (Ngo et al., 2020). These dynamics are described as thalamo-cortical spindles, hippocampal ripples, and cortical slow oscillations (Latchoumane et al., 2017). Hippocampal ripples, or brief periods of synchronized oscillatory activity, are thought to facilitate communication between the hippocampus and cortical and subcortical regions (Todorova & Zugaro, 2020; Brodt et al., 2023). 

The neural mechanism by which these dynamics may enable memory consolidation is through phase-locking of brain activity between different brain areas, enabling the transmission and nesting of neural signals between brain regions. Animal research has shown that when hippocampal ripples are disrupted, memory consolidation is impaired (Ego-Stengel & Wilson, 2010).

Can memory be enhanced during sleep?

Studies investigating what happens when we disrupt SWS in human and non-human animals have shown that disruption of oscillatory dynamics during SWS can lead to deficits in memory tasks.  But what about the possibility of enhancing memory through sleep?

In a recent study, Geva-Sagiv and colleagues performed closed-loop brain stimulation during sleep in human patients implanted with intracranial electrodes (Geva-Sagiv et al., 2023). The participants performed a cognitive memory task, by which memory accuracy was compared following natural sleep and sleep during which closed-loop stimulation was precisely applied during active phases of SWS. They found enhanced sleep spindles and synchronized spiking between interconnected brain regions following stimulation SWS. Additionally, stimulation during SWS correlated with improved memory accuracy in the behavioral task. These data suggest that the synchronized brain activity during SWS can be increased via external stimulation, correlating with enhanced memory consolidation.  

What’s next?

Sleep-related memory enhancement has enormous implications for clinical application. Sleep deprivation is incredibly detrimental to human health, for both the brain and the body. Insight from sleep research can enable improved treatment for the effects of sleep deprivation and insomnia, as well as the many disorders where sleep disruption occurs. Further research will help to progress our understanding of sleep-related memory enhancement, and how it can be used to make an impact in the future.

References +

Krause et al., 2017. The sleep-deprived human brain. Nature Reviews Neuroscience.

Nunn & Samson, 2018. Sleep in a comparative context: Investigating how human sleep differs from sleep in other primates. American Journal of Physical Anthropology.

Nunn et al., 2016. Shining evolutionary light on human sleep and sleep disorders. Evolution, Medicine, and Public Health.

Klinzing et al., 2019. Mechanisms of system memory consolidation during sleep. Nature Neuroscience.

Ngo et al., 2020. Sleep spindles mediate hippocampal-neocortical coupling during long-duration ripples. eLife.

Latchoumane et al., 2017. Thalamic Spindles Promote Memory Formation during Sleep through Triple Phase-Locking of Cortical, Thalamic, and Hippocampal Rhythms.

Todorova & Zugaro, 2020. Hippocampal ripples as a mode of communication with cortical and subcortical areas.

Brodt et al., 2023. Sleep-A brain-state serving systems memory consolidation. Neuron.

Geva-Sagiv et al., 2020. Augmenting hippocampal-prefrontal neuronal synchrony during sleep enhances memory consolidation in humans. Nature Neuroscience.