Does Marijuana Harm the Brain?
Have a question about science, health, fitness, or diet? Get cited, evidence-based insights: Consensus is an AI-Powered Academic Search Engine.
Try for freeCheck out this answer from Consensus:
While marijuana is often perceived as a harmless drug, growing evidence suggests that its use can have adverse effects on brain health. Acute and chronic marijuana use is associated with cognitive impairments, structural and functional brain alterations, and disrupted neurophysiological signals. Although some cognitive deficits may recover after abstinence, the long-term impact on brain function and the potential for neuronal recovery require further investigation. As marijuana use continues to rise, it is crucial for healthcare providers and consumers to be informed about its potential risks to brain health.
Marijuana, also known as cannabis, is one of the most widely used psychoactive substances globally. With changing legal and societal views, understanding its impact on brain health has become increasingly important. This article explores the effects of marijuana on brain structure, function, and cognition, drawing on findings from multiple research studies.
Effects on Cognitive Function
Several studies have investigated the impact of marijuana on cognitive functions such as memory, attention, and executive functions. Acute marijuana use has been shown to impair working memory (WM) and episodic memory (EM), with users displaying slower and less accurate responses in cognitive tasks1. A systematic review of neurocognitive effects found that cannabis intoxication leads to small to moderate deficits in various cognitive domains, including executive functions, learning, memory, and attention5. These impairments can persist beyond the period of acute intoxication, suggesting residual effects on cognitive function.
Brain Structure and Function
Research on the structural and functional changes in the brain due to marijuana use has yielded mixed results. Some studies have reported abnormalities in hippocampus volume and gray matter density among regular cannabis users2. Functional neuroimaging studies have shown altered patterns of brain activity, particularly in regions associated with cognitive control and reward processing4. For instance, decreased activation in the anterior cingulate cortex and dorsolateral prefrontal cortex has been observed, which are linked to cognitive control and attention-related processes4.
Neurophysiological Changes
Marijuana use affects neurophysiological signals, as evidenced by changes in EEG recordings. Acute marijuana smoking has been associated with decreased global theta band EEG power and reduced alpha band EEG reactivity, indicating disrupted attention processes1. Additionally, marijuana use has been linked to changes in regional cerebral blood flow (rCBF), with increased rCBF in certain brain regions and decreased rCBF in others, potentially underlying perceptual and cognitive alterations3.
Long-term Effects and Recovery
The long-term effects of heavy and dependent cannabis use on the brain are still not fully understood. Some evidence suggests that cognitive impairments, particularly in learning and memory, may recover after a period of abstinence9. However, the extent and time course of neuronal recovery remain unclear. Moreover, the impact of cannabis on brain health may be moderated by factors such as age of onset, heaviness of use, and the presence of comorbid psychiatric disorders9.
Mechanisms of Action
The primary psychoactive constituent of marijuana, delta-9-tetrahydrocannabinol (Δ9-THC), activates cannabinoid receptors in the brain, which are abundant in regions involved in cognition and behavior. This activation can disrupt neurotransmitter release, synaptic plasticity, and neurodevelopment, leading to cognitive and behavioral abnormalities8. Additionally, Δ9-THC may indirectly affect dopamine firing by altering glutamate neurotransmission, further contributing to its psychotomimetic effects10.
Does marijuana harm the brain?
Justine Renard has answered Near Certain
An expert from University of Western Ontario in Neuroscience
If we speak about marijuana strains containing high levels of THC (the psychoactive component of marijuana), YES, it can be harmful, especially if used during the vulnerable period of adolescence. Several preclinical and clinical studies have reported that THC use occurring before age of 17 can increase the risk of developing important cognitive deficits and psychiatric disorders in adulthood, including anxiety, depression, and schizophrenia. This is due to the highly vulnerable adolescent brain development period which involves colossal synaptic and neuronal reorganisations to support adult emotional, cognitive and affective processing. THC acts on CB1 receptors, which play a critical role during neurodevelopment, in controlling maturational and neuronal processes. THC-induced changes in CB1Rs signaling during adolescence can have profound persistent drastic consequences on functioning in the adult brain which may underlie a plethora of potential neuropsychiatric disturbances in later life. On the other hand, the main non-psychoactive compound of marijuana, cannabidiol (CBD) has opposite effects of THC on neuropsychiatric disorders: Whereas THC is mainly associated with psychotic effects and the onset of psychiatric diseases, CBD on the contrary, possesses antipsychotic effects. Indeed, recent evidence has demonstrated that CBD can, not only counteract the psychotomimetic properties of THC, and improve psychosis symptoms in schizophrenia patients, but CBD has also a neuropharmacological profile similar to atypical antipsychotics without inducing deleterious side effect.
Therefore, it would be probably safer for the adolescent brains to be rather exposed to marijuana strains containing much lower THC and higher CBD levels. This would probably lead to fewer psychosis-like symptoms and lower risk for developing psychiatric diseases.
REFERENCES
-Renard J, Rushlow WJ, Laviolette SR. What can rats tell us about adolescent cannabis exposure? Insights from. Can J Psychiatry (2016) 61:328–334. doi:10.1177/0706743716645288
-Renard J, Loureiro M, Rosen LG, Zunder J, de Oliveira C, Schmid S, Rushlow WJ, Laviolette SR. Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway. J Neurosci (2016) 36:5160–9. doi:10.1523/JNEUROSCI.3387-15.2016
-Renard J, Vitalis T, Rame M, Krebs MO, Lenkei Z, Le Pen G, Jay TM. Chronic cannabinoid exposure during adolescence leads to long-term structural and functional changes in the prefrontal cortex. Eur Neuropsychopharmacol (2016) 26:55–64. doi:10.1016/j.euroneuro.2015.11.005
doi:10.1016/j.euroneuro.2015.11.005
-Renard J, Rosen LG, Loureiro M, De Oliveira C, Schmid S, Rushlow WJ, Laviolette SR. Adolescent Cannabinoid Exposure Induces a Persistent Sub-Cortical Hyper-Dopaminergic State and Associated Molecular Adaptations in the Prefrontal Cortex. Cereb Cortex (2016) doi:10.1093/cercor/bhv335
-Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ (2002) 325:1212–1213. doi:10.1136/bmj.325.7374.1212
-Andréasson S, Allebeck P, Engström A, Rydberg U. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet (1987) 2:1483–1486. doi:10.1016/S0140-6736(87)92620-1
-Stefanis NC, Delespaul P, Henquet C, Bakoula C, Stefanis CN, Van Os J. Early adolescent cannabis exposure and positive and negative dimensions of psychosis. Addiction (2004) 99:1333–1341. doi:10.1111/j.1360-0443.2004.00806.x
– Renard J, Krebs M, Pen G Le, Jay TM. Long-term consequences of adolescent cannabinoid exposure in adult psychopathology. Front Neurosci (2014) 8:1–14. doi:10.3389/fnins.2014.00361
-Andersen SL. Trajectories of brain development: Point of vulnerability or window of opportunity? in Neuroscience and Biobehavioral Reviews, 3–18. doi:10.1016/S0149-7634(03)00005-8
-Spear LP. The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev (2000) 24:417–463.
-Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkötter J, Hellmich M, Koethe D. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry (2012) 2:e94.
Does marijuana harm the brain?
Charles Ksir has answered Uncertain
An expert from University of Wyoming in Neuroscience
The arguments that marijuana use can “harm” the brain are based on two kinds of arguments. One: CBD receptors are affected by the drug and are important, especially during development. Yes, THC acts on these important systems but that does not mean the brain is “harmed”. Some of the same people who make this argument will prescribe drugs that have profound influences on serotonin, GABA, dopamine, etc and they seem to be less concerned about the long-term consequences of those drug exposures during development, for reasons that elude me. Two: marijuana users are statistically more likely to also have other behavioral problems (poor school performance, more psychopathology). This is a correlational relationship and it is not at all clear that marijuana use is responsible for these other issues. People who are vulnerable to a variety of behavioral problems are more likely to also use marijuana, use more marijuana, use the more potent forms–but also more likely to misuse other substances. It is not logical to conclude that marijuana causes these problems just because in many cases the same people exhibit both kinds of problem behavior.
Does marijuana harm the brain?
Robert Carson has answered Near Certain
An expert from Vanderbilt University in Epileptology, Neuroscience, Neurology
The key difference between a medicine and a poison is the dose. As others have stated, all drugs have the potential for side effects, with even the difference between good side effects and bad side being in the eye of the beholder. Many of use would frown at taking a medicine that causes weight gain. But, if you cannot put on weight or have decreased appetite for another medical reason, then increased appetite is a good thing.
We continue to learn more about Cannabis and the potential benefits from specific molecules in the plant. Cannabidiol (CBD) is now established as a bona fide treatment for severe epilepsy. That being said, there is data that supports detrimental effects of long-term Cannabis use.
Meier et al. reported in 2012 a prominent IQ drop in people who started using cannabis as a teen and continued to use over time. Like with other studies, there is the potential for confounding factors in such a study. In a response to commentaries expressing concern about this, when additional controls for socio-economic status were done, the IQ decrease was still present (Moffitt et al. 2013). In an interesting follow-up study, the same group reported that over a shorter time frame, from age 12-18, there was not a decline in IQ, but interestingly, IQs were lower in the teens who used cannabis versus those that did not both prior to and after using cannabis(Meier et al. 2018).
This data is consistent with other studies showing deficits in working memory and with MRI studies showing decreased thickness in regions of the hippocampus, a brain region key for memory formation, in adults with a history of heavy cannabis use (Chye et al. 2017, Owens et al. 2019). On average, college students who report cannabis use have lower grade-point averages than those who do no t(Martinez et al. 2015). Consistent with the reports above, a randomized controlled-trial of cannabis has been done in adults and demonstrated decreased verbal memory and working memory after smoking cannabis (Hindocha et al. 2017).
I like to point out that in one of the studies noted above, the reported IQ drop was 8 points. If you are a rare human with a genius IQ in the 170’s and lose 8 IQ points, you would still be a genius. If you are a mere average human with an IQ of 100, loss of 8 IQ points may have notable consequences.
Does marijuana harm the brain?
Nadia Solowij has answered Likely
An expert from University of Wollongong in Cannabis
Likely – if used heavily over a prolonged period of time.
While the evidence base for structural changes to the brain is mixed, many studies have consistently found that long-term very heavy cannabis users have smaller volumes of certain regional structures within the brain, with the hippocampus – a region involved in memory function – most consistently affected.
Given the absence of longitudinal studies, that follow people over many years from before they started using cannabis to decades into their cannabis use, we cannot know for certain whether it may be that cannabis users had smaller hippocampal volumes prior to using cannabis and whether this could represent a vulnerability to extensive use. However associations between the extent of cannabis use – number of years used, frequency/quantity of use, and particularly now, dependence on cannabis – and brain structural changes have been found. Similarly for the function of the brain, whether examined by brain imaging methods or traditional cognitive/neuropsychological tests – long term heavy cannabis users are typically impaired in memory function, also attention, decision making, planning etc.
There is evidence that these cognitive and brain functional and structural impairments can improve or revert to normal after a period of abstinence from cannabis, but the evidence is not definitive and there is also evidence of subtle functional alterations to the brain persisting for some time beyond cessation of use. There are also question marks around particular periods of vulnerability to brain harms from exposure to cannabis, for example adolescence when the brain is undergoing many changes toward maturation.
Most of the harms to the brain, even if they are reversible (and there is no reason to suspect that they are permanent), have been found to be associated with exposure to THC – emerging evidence that is really interesting is that CBD may actually protect the brain from the harms associated with THC, and there is significant research ongoing to understand the interaction of these two compounds (and others from the multitude of compounds within cannabis), and their relative proportions or ratios within cannabis.
Of note too, there is substantial evidence from animal research for harms to the brain from exposure to THC, but also exciting growing evidence that CBD may have a range of benefits for brain structure and function in various disease models – not in healthy animals or humans – so we need to be cautious and wary with regard to the proliferation of CBD products used in the general community.
Does marijuana harm the brain?
Maria-Paz Viveros has answered Near Certain
An expert from Complutense University of Madrid in Neurobiology, Addiction, Physiology
The main psychoactive compound of cannabis (marijuana) is the Delta-9-tetrahydrocannabinol (THC) that exerts its effects when activating cannabinoid receptors. The CB1 cannabinoid receptor is one of the most abundant receptors in the brain. Cannabinoid receptors are found not only in the nervous system but also in other systems and therefore the harmful effects of cannabis refer not only to the nervous system and behavior but also to other functions. Here I will focus on its effects on brain and behaviour.
Marijuana has been associated with disrupted functioning in a variety of cognitive and performance tasks, and chronic marijuana smoking has been reported to cause persistent memory deficiencies. In addition, pharmacological studies have shown that cannabinoids can induce a full range of transient positive, negative, and cognitive symptoms in healthy individuals that are similar to those seen in schizophrenia. Moreover, there is also increasing evidence indicating a close relationship between cannabis consumption and an increased risk for depression, anxiety disorders, and drug addiction.
To understand these effects, it is essential to take into account that the endocannabinoid (ES) system (which includes the cannabinoid receptors, the endogenous ligands of these receptors and the enzymatic machinery for their synthesis and degradation) is a neuromodulatory system that plays a very important role in various aspects of the psychophysiology of the individual, including regulation of anxiety and response to stress, energy balance and reward systems of the brain. It is also essential to highlight that in both the rodent and the human foetal brain, cannabinoid receptors are present from early developmental stages onwards and the ES plays an important role in brain development. So, it is logical that the interference with the modulatory role of the ES by THC consumption can alter brain development and induce enduring adverse effects. Two critical periods for neurodevelopment are the perinatal and adolescent periods. During these stages, the brain shows a unique plasticity and is especially vulnerable to the action of cannabis (and other drugs of abuse). Moreover, the ES itself is in full development during these developmental phases, therefore the consumption of cannabis which implies the repeated activation of the receptor CB1 by THC can interfere with the development of the ES and alter its regulatory functions.
Cannabis sativa preparations are among the illicit drugs most commonly used by young people, including pregnant women. Data from epidemiological studies in humans as well as studies in experimental animals indicate that prenatal/perinatal exposure to cannabis affects brain development and may have long-term effects on cognitive function and other aspects of behaviour, notably emotional aspects and affectation of the reward system of the brain. Investigations using animal models provide useful information for a better understanding of the long-lasting deleterious consequences of cannabis exposure during pregnancy and lactation. It is important to emphasize that THC is able to cross the placental barrier and to be secreted in breast milk. As mentioned above, adolescence is another critical neurodevelopmental period during which brain shows a special plasticity.
The maturational processes that occur in the brain during adolescence are likely to confer a higher risk for suffering from adverse consequences of cannabinoid exposure. In fact, increasing use of cannabis among adolescents is a matter of great public concern that has led to a parallel increase in research on appropriate animal models. Chronic administration of cannabinoid agonists during the peri-adolescent period causes persistent behavioural alterations related to cognitive deficits, increased risk of psychosis, mood disorders and addiction to cannabis and other drugs of abuse. In addition to the age of onset, other factors such as genetic vulnerability, dosing, personality traits and amount of THC present in the drug are also important factors that may influence the impact of drug use. The content of THC in confiscated cannabis preparations has substantially increased over the past 20 years. A potent variant termed sinsemilla or skunk has become available in many countries. Moreover, there is growing public health concern about the increasing use of a new generation of highly potent and dangerous synthetic cannabinoid ,agonists. Thus, cannabis consumption nowadays may imply exposure to very high amounts of THC, especially if sinsemilla (skunk) or synthetic cannabinoids are consumed. As mentioned above, the genetic background might be a crucial factor in terms of vulnerability, but we are still far from having a clear knowledge about the nature of the genes implicated and from predicting and controlling these risk factors. Therefore, it seems clear that the best strategy is abstinence.
Giving healthy alternatives to young people, promoting exercise and considering that availability of the drug might be another risk factor, are all important aspects to establish efficacious treatment and prevention campaigns.
References:
– Calvigioni D, Hurd YL, Harkany T, Keimpema E. Neuronal substrates and functional consequences of prenatal cannabis exposure. Eur Child Adolesc Psychiatry. 2014 Oct;23(10):931-41.
-De Aquino JP, Sherif M, Radhakrishnan R, Cahill JD, Ranganathan M, D’Souza DC. The Psychiatric Consequences of Cannabinoids. Clin Ther. 2018 Apr 17. pii: S0149-2918(18)30106-1. doi: 10.1016/j.clinthera.2018.03.013. [Epub ahead of print] PubMed PMID: 29678279.
– Renard J, Rushlow WJ, Laviolette SR. What Can Rats Tell Us about Adolescent Cannabis Exposure? Insights from Preclinical Research. Can J Psychiatry. 2016 Jun;61(6):328-34.
– Viveros MP and Marco EM Age-Dependent Effects of Cannabinoids on Neurophysiological, Emotional, and Motivational States, In: © Springer Science+Business Media New York 2015, P. Campolongo, L. Fattore (eds.), Cannabinoids and Modulation of Emotion, Memory, and Motivation, DOI 10.1007/978-1-4939-2294-9_11 Chapter 11
-for other research articles by Viveros MP, please see:
https://orcid.org/0000-0002-4119-4636
PubMed: search as Viveros MP
-Highly recomended web:-National Institute on Drug Abuse (NIDA) http://www.drugabuse.gov
Does marijuana harm the brain?
Matthijs Bossong has answered Likely
An expert from University Medical Center Utrecht in Psychiatry, Neuroimaging, Pharmacology
From a biological point of view, I would say yes. The endogenous cannabinoid system (consisting of cannabinoid receptors and cannabis-like like substances binding to these receptors) is one of the most important neurotransmitter systems in the brain. Its main function is to regulate the release of other neurotransmitters such as GABA and glutamate. It thereby plays an important role in brain development, mood, cognition, etc. The use of an external substance such as marijuana (or in fact THC, the most important psychoactive component of marijuana, which acts on cannabinoid receptors), will interfere with the normal function of this endocannabinoid system. This may thus have an effect on for example brain development, mood, cognition, etc. Obviously the degree of the impact depends on factors such as dose and frequency, but also age. There is quite some evidence that the harmful effects of cannabis are most severe when it is used during adolescence, one of the most important eras of brain development (Bossong and Niesink, 2010).
A lot of research focussed on the effects of cannabis on psychosis and cognition. Regarding the residual effects of cannabis use on cognition, i.e. those effects that persist after acute intoxication, meta-analyses found evidence for mild cognitive impairments, in for example learning, memory and executive function, which were particularly associated with frequent or heavy cannabis use. Importantly, these effects attenuated with prolonged abstinence, suggesting recovery from the residual cognitive impact of cannabis use (Grant et al., 2003; Schreiner and Dunn, 2012; Scott et al., 2018). Regarding the association between cannabis use and the later development of a psychotic disorder, epidemiological studies indicate that the use of cannabis increases the risk for developing a psychotic disorder such as schizophrenia (Moore et al., 2007; Marconi et al., 2016; Vaucher et al., 2018). This risk particularly increases with a younger age of onset of cannabis use, a higher frequency of use, and the use of more potent cannabis (more THC, ‘skunk’) (Di Forti et al., 2009; 2014).
As a final remark I would like to state that this does not imply that people cannot benefit from the effects of cannabis. Most adverse effects occur with frequent or heavy use, and there are situations where the beneficial effects may overcome the potential risks. Also, particular individual compounds in cannabis, such as cannabidiol, may have important therapeutic potential for example as antipsychotic medication (Iseger and Bossong, 2015).
Does marijuana harm the brain?
Abbas Khani has answered Near Certain
An expert from University of Geneva in Neuroscience
The short answer is “Yes, it definitely does”. While there are controversies around the effects of cannabis consumption on brain, there are numerous studies suggesting altered cognition and decision making following consumption of marijuana. These disrupting effects have been reported in both recreational and chronic users and among adolescents and adults. We have shown (Khani et al. 2015, Psychopharmacology; for a review see cannabinoids section in Khani and Rainer, 2016, Journal of Neurophysiology) that local administration of cannabinoid agents into the brain areas that govern decision making, changed the pattern of decision making such that the rats were more impulsive (preferring immediate small reward for a delayed large reward) and were less willing to expend effort to achieve a higher amount of reward. The effects of marijuana consumption needs further research taking into account the impact of dose, frequency and duration of consumption.
Does marijuana harm the brain?
Andra Smith has answered Near Certain
An expert from University of Ottawa in Neuroscience
Just to be clear, we are talking about THC here rather than CBD (cannabidiol). The evidence is quite clear that THC impacts the developing brain negatively if use begins early (before 18) and is regular (meaning at least once a week for a few years). We do not know enough about occasional use to say we really understand its impact. The issue there is that it is difficult to know if there is a genetic predisposition to either addiction or other mental health issues like psychosis. Often it is too late once that is figured out.
Biology does not know the difference between a legal or non-legal drug so just because something is legal does not mean it is harmless. Just because it is a natural plant also does not mean it is harmless. Heroin comes from a plant, as does tobacco. No one would smoke a substance from poison ivy would they!
Our brain imaging research shows significantly altered brain activity in several brain regions during executive functioning (cognitive processing like response inhibition or working memory) in teen cannabis users compared to non-users. These were teens who had used at least once/week for at least 3 years (Hatchard et al., 2014; http://dx.doi.org/10.4172/2155-6105.1000197, Smith et al., 2010; DOI 10.1007/s00213-010-1841-8, Smith et al., 2011; doi:10.4236/jbbs.2011.13017).
This is consistent with other imaging work, again showing early exposure has a more significant impact on higher order cognition than non-exposure.
Does marijuana harm the brain?
Nosarieme Abey has answered Likely
An expert from University of Lagos in Nutrition, Neuroscience
Let me start by quoting Douglas et al., 2008; the brain is deeply complex, mysterious, and delicately balanced, any chemical added to its mix disrupts its normal functions.
- Marijuana contains more than 400 chemicals, Psychoactive agent = ∆9 Tetrahydrocannabinol (THC).
- Endocannabinoids are naturally-occurring, they bind to Cannabinoid receprtors (CB1 and CB2, to cause dowstream effects. Like other psychoactive drugs, THC activates neurons because its chemical structure mimics the natural neurotransmitters and can therefore directly and indirectly target the brain’s reward system by flooding the circuit with dopamine.
- Tetrahydrocannabinol (THC) acts on cannabinoid receptors which are found on neurons in many places in the brain. These brain areas are involved in memory (the hippocampus), concentration (cerebral cortex), perception (sensory portion of the cerebral cortex), and movement (the cerebellum).
- Cognition is a faculty for the processing of information, applying knowledge, and changing preferences. Learning involves the brain processing information in complex networks of nerve cells. The brain cells communicate and excite one another through special connections, called synapses. Researchers have found that THC changes the way in which sensory information gets into and is acted on by the hippocampus. THC at high concentrations over a period time can cause competitive inhibition of the AChE enzyme and inhibition of β-amyloid peptide aggregation, implicated in the development of Alzheimer’s disease (Eubanks et al., 2006).
- Biochemically, Cannabis use caused cellular damage through mediation of imbalance in the normal neurotransmission system; this depends importantly on the dose and duration of exposure. Heavy cannabis users are at higher risks of cognitive function impairment and mood disorder.
REFERENCES
Douglas, RJ; Martin, KA (2004). “Neuronal circuits of the neocortex”. Annual Review of Neuroscience 27: 419–451.
Eubanks, Lisa M.; Rogers, Claude J.; Beuscher, 4th; Koob, George F.; Olson, Arthur J.; Dickerson, Tobin J.; Janda, Kim D. (2006). “A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology”. Molecular Pharmaceutics 3 (6): 773–7
Abey Nosarieme omoregie Cannabis sativa (Marijuana) alters blood chemistry and the cytoarchitecture of some organs in Sprague Dawley rat models, Food and Chemical Toxicology Volume 116, Part B, June 2018, Pages 292-297.
Does marijuana harm the brain?
Kumar Vaibhav has answered Likely
An expert from Augusta University in Neurochemistry, Neuroimaging, Neurology, Neurobiology, Neuroscience, Neuropsychology
Cannabis (marijuana) is a complex plant containing over 400 chemical entities, with major compounds such as delta-9-tetrahydrocannabinol (THC) and cannabidiol.1 The discovery of plant cannabinoids led to the identification of endocannabinoid system (ECS) that is considered to be responsible for numerous significant physiological and immune functions. There has been a recently consistent worldwide increase in cannabis use, with increasing associated health concerns. Several studies have shown cannabis-induced increased risk of developing psychotic illness.2-4 However, variability of cannabinoid contents in cannabis products and individual’s receptiveness to cannabis effect show varied responses in different cases. Therefore, in this report, we will first explore ECS and its ligands with published literature to better understand the effects of marijuana on human brain.
The ECS is comprised of two primary endocannabinoid receptors (CB1R and CB2R). CB1R is detected mainly in the CNS on certain types of neurons and mediates the psychoactive effects of marijuana.5-7 Conversely, CB2R is predominantly expressed on immune cells (lymphocytes, monocytes, macrophages) and endothelial cells in both rodents and humans.8 Bioactive endocannabinoid ligands that may be synthesized by multiple cell types within the CNS.9, 10 The ECS influences a variety of physiological systems that are dysregulated after injury, including memory function, appetite, mood, pain sensation, and immune activation.10,5 In addition, activation of non-psychoactive CB2R were recently implicated in improved cerebral perfusion via an undefined mechanisms that involve reduced inflammation.5, 9-12 Endocannabinoids are arachidonate based lipids (Eicosanoids), such as anandamide (N-arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG), that serve as physiological ligands for the cannabinoid receptors (CB1R and CB2R)5, 6 and are released within the injured CNS to as a response.5, 7, 13-23 Consistent with this assertion, stimulation of CB2R not CB1R reduced inflammation, protected both vascular integrity, and limited disruption of the blood-brain barrier (BBB).7, 16, 17 Moreover, CB2R activation is associated with protective anti-inflammatory effects in animal models for atherosclerosis,18 multiple sclerosis,19 Alzheimer disease,20 and arthritis.21 However, the primary psychoactive ingredient in cannabis, THC, affects the brain mainly by activating CB1R. CB1R is expressed at high levels in many brain regions, and several endogenous brain lipids have been identified as CB1R ligands. Endocannabinoids are released from postsynaptic neurons and activates CB1R on presynaptic axons thus, suppressing neurotransmitter release. Cannabinoids may affect memory, cognition, and pain perception by means of this cellular mechanism.24
Cannabis active ingredient, THC is the most commonly abused neuroactive substance, among young adults. Study by Abey 25 revealed a dose-dependent decline in the cognitive function, statistically significant decrease in the brain total protein content, cardiac hypertrophy, neuronal hyper-cellularity, prominent sinusoids in liver and vascular congestion in testes in cannabis fed rats. Another study on Cannabis users exhibited poorer learning and dementia. Also, cannabis users had slower reaction times and attention deficits.26 Multiple cases of ischemic and hemorrhagic strokes associated with cannabis use have been reported in the literature.27-29 It has been suggested that cannabis can affect cerebral auto-regulation and vascular tone leading to vasoconstriction and acute ischemic stroke. Additionally, patient with a history of heavy cannabis use, developed a rapid hemorrhage following thrombolytic therapy for ischemic stroke. 29 Further, chronic cannabis users showed greater emotional deficits.30 Thus, Cannabis use caused cellular damage through mediation of imbalance and altered cytoarchitecture which may affects the overall health of dependent user.
According to the 2015 National Survey on Drug Use and Health, cannabis (marijuana) is the most commonly used recreational drug in the US. Among pregnant women aged 14-55 years, 3.4% were cannabis users. AEA exposure during pregnancy appears to affect fetal viability and postnatal weight gain in the pup brain.31 There are three primary findings related to age of first use of marijuana. Adolescent subjects showed more reduced cortical gray matter than adult ones. Functionally, adolescent males and females were physically smaller and having high CBF, with the effects being greater in males.32
It is obvious cannabinoid exposure can have lasting effects on the brain and behavior, but it is not yet clear which brain changes underlie the effects of cannabinoid exposure on drug self-administration. The influence of variables such as genetic strain, sex, and age during cannabinoid exposure have been varied systematically in some studies where brain changes were observed, but there is a general need for more cannabinoid exposure experiments that directly compare the effects of these variables on drug self-administration. It would also be informative to explicitly compare the effects of exposure to cannabis, THC, and synthetic cannabinoids. Probably because of the difficulty of studying cannabinoid reward in animals, the possibility that previous exposure to non-cannabinoid drugs can alter cannabinoid reward remains to be explored. Finally, it should be noted that the simultaneous use of cannabis with other drugs might enhance the rewarding effects of cannabis or the other drugs, and that this simultaneous use could potentially have more impact than prior exposure to cannabis. For example, tobacco is often used together with cannabis with the goal of enhancing the rewarding effects of cannabis33, and 75% of cannabis users report that their first use of cannabis involved co-use of another drug.34 The important question is whether simultaneous use of cannabis and other drugs increases the likelihood of addiction, that should be studied systematically under controlled conditions.
Cannabis has become increasingly accepted for both recreational and medicinal purposes. Without reliable information about the effects of cannabis, people cannot make informed decisions regarding its use. Like alcohol and tobacco, cannabis can have serious adverse effects on health and has a potential to turn users addicted to other drugs. The natural cannabinoid system of the brain is a highly complex regulatory system that controls brain development, reward, emotion, and cognition. The current scientific research provides us important information on ECS: (1) mechanism of cannabis effect on brain and behavior, and (2) whether cannabis might produce chronic brain alteration that increase the likelihood of becoming addicted. Although the health benefits of medical marijuana are becoming better understood, more research is needed to understand the chronic and acute effects of marijuana. In response to question asked here “Does marijuana harm the brain?”, the answer is “Most likely it does”. However, the effect of marijuana depends on amount of its dominant constituents (THC, cannabidiol etc.) in consumables and the period of continuous use. More addictive and psychotropic effect might be observed with chronic use of marijuna. Therefore, intervention and prevention programs must better address potential effects of marijuana and its constituents (THC and cannabidiol etc.) on brain while acknowledging its beneficial effect.
- Atakan Z. Cannabis, a complex plant: Different compounds and different effects on individuals. Therapeutic advances in psychopharmacology. 2012;2:241-254
- Hall W, Degenhardt L. Prevalence and correlates of cannabis use in developed and developing countries. Current opinion in psychiatry. 2007;20:393-397
- Degenhardt L, Coffey C, Carlin JB, Swift W, Moore E, Patton GC. Outcomes of occasional cannabis use in adolescence: 10-year follow-up study in victoria, australia. The British journal of psychiatry : the journal of mental science. 2010;196:290-295
- Panlilio LV, Justinova Z. Preclinical studies of cannabinoid reward, treatments for cannabis use disorder, and addiction-related effects of cannabinoid exposure. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2018;43:116-141
- Buch SJ. Cannabinoid receptor 2 activation: A means to prevent monocyte-endothelium engagement. The American journal of pathology. 2013;183:1375-1377
- Ashton CH, Moore PB. Endocannabinoid system dysfunction in mood and related disorders. Acta psychiatrica Scandinavica. 2011;124:250-261
- Ramirez SH, Hasko J, Skuba A, Fan S, Dykstra H, McCormick R, et al. Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2012;32:4004-4016
- Anday JK, Mercier RW. Gene ancestry of the cannabinoid receptor family. Pharmacological research. 2005;52:463-466
- Amenta PS, Jallo JI, Tuma RF, Elliott MB. A cannabinoid type 2 receptor agonist attenuates blood-brain barrier damage and neurodegeneration in a murine model of traumatic brain injury. Journal of neuroscience research. 2012;90:2293-2305
- Benyo Z, Ruisanchez E, Leszl-Ishiguro M, Sandor P, Pacher P. Endocannabinoids in cerebrovascular regulation. American journal of physiology. Heart and circulatory physiology. 2016;310:H785-801
- Rom S, Zuluaga-Ramirez V, Dykstra H, Reichenbach NL, Pacher P, Persidsky Y. Selective activation of cannabinoid receptor 2 in leukocytes suppresses their engagement of the brain endothelium and protects the blood-brain barrier. The American journal of pathology. 2013;183:1548-1558
- Braun M, Khan ZT, Khan MB, Kumar M, Ward A, Achyut BR, et al. Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization. Brain, behavior, and immunity. 2017
- Guo S, Liu Y, Ma R, Li J, Su B. Neuroprotective effect of endogenous cannabinoids on ischemic brain injury induced by the excess microglia-mediated inflammation. American journal of translational research. 2016;8:2631-2640
- Szczesniak AM, Porter RF, Toguri JT, Borowska-Fielding J, Gebremeskel S, Siwakoti A, et al. Cannabinoid 2 receptor is a novel anti-inflammatory target in experimental proliferative vitreoretinopathy. Neuropharmacology. 2017;113:627-638
- Zurier RB, Burstein SH. Cannabinoids, inflammation, and fibrosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2016;30:3682-3689
- Miller AM, Stella N. Cb2 receptor-mediated migration of immune cells: It can go either way. British journal of pharmacology. 2008;153:299-308
- Facchinetti F, Del Giudice E, Furegato S, Passarotto M, Leon A. Cannabinoids ablate release of tnfalpha in rat microglial cells stimulated with lypopolysaccharide. Glia. 2003;41:161-168
- Rajesh M, Mukhopadhyay P, Batkai S, Patel V, Saito K, Matsumoto S, et al. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. Journal of the American College of Cardiology. 2010;56:2115-2125
- Benito C, Romero JP, Tolon RM, Clemente D, Docagne F, Hillard CJ, et al. Cannabinoid cb1 and cb2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27:2396-2402
- Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML. Prevention of alzheimer’s disease pathology by cannabinoids: Neuroprotection mediated by blockade of microglial activation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2005;25:1904-1913
- Mbvundula EC, Bunning RA, Rainsford KD. Arthritis and cannabinoids: Hu-210 and win-55,212-2 prevent il-1alpha-induced matrix degradation in bovine articular chondrocytes in-vitro. The Journal of pharmacy and pharmacology. 2006;58:351-358
- Downer EJ, Clifford E, Gran B, Nel HJ, Fallon PG, Moynagh PN. Identification of the synthetic cannabinoid r(+)win55,212-2 as a novel regulator of ifn regulatory factor 3 activation and ifn-beta expression: Relevance to therapeutic effects in models of multiple sclerosis. The Journal of biological chemistry. 2011;286:10316-10328
- Lourbopoulos A, Grigoriadis N, Lagoudaki R, Touloumi O, Polyzoidou E, Mavromatis I, et al. Administration of 2-arachidonoylglycerol ameliorates both acute and chronic experimental autoimmune encephalomyelitis. Brain research. 2011;1390:126-141
- Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain. Science (New York, N.Y.). 2002;296:678-682
- Abey NO. Cannabis sativa (marijuana) alters blood chemistry and the cytoarchitecture of some organs in sprague dawley rat models. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2018;116:292-297
- Lovell ME, Bruno R, Johnston J, Matthews A, McGregor I, Allsop DJ, et al. Cognitive, physical, and mental health outcomes between long-term cannabis and tobacco users. Addictive behaviors. 2018;79:178-188
- Goyal H, Awad HH, Ghali JK. Role of cannabis in cardiovascular disorders. Journal of thoracic disease. 2017;9:2079-2092
- Goyal H, Singla U, Gupta U, May E. Role of cannabis in digestive disorders. European journal of gastroenterology & hepatology. 2017;29:135-143
- Shere A, Goyal H. Cannabis can augment thrombolytic properties of rtpa: Intracranial hemorrhage in a heavy cannabis user. The American journal of emergency medicine. 2017;35:1988.e1981-1988.e1982
- Zimmermann K, Walz C, Derckx RT, Kendrick KM, Weber B, Dore B, et al. Emotion regulation deficits in regular marijuana users. Human brain mapping. 2017;38:4270-4279
- Amlani A, Hornick MG, Cooper K, Prazad P, Donovan R, Gulati A. Maternal cannabinoid use alters cannabinoid (cb1) and endothelin (etb) receptor expression in the brains of dams but not their offspring. Developmental neuroscience. 2017;39:498-506
- Wilson W, Mathew R, Turkington T, Hawk T, Coleman RE, Provenzale J. Brain morphological changes and early marijuana use: A magnetic resonance and positron emission tomography study. Journal of addictive diseases. 2000;19:1-22
- Amos A, Wiltshire S, Bostock Y, Haw S, McNeill A. ‘You can’t go without a fag…You need it for your hash’–a qualitative exploration of smoking, cannabis and young people. Addiction (Abingdon, England). 2004;99:77-81
- Olthuis JV, Darredeau C, Barrett SP. Substance use initiation: The role of simultaneous polysubstance use. Drug and alcohol review. 2013;32:67-71
Does marijuana harm the brain?
Paul Morrison has answered Unlikely
An expert from King’s College London in Psychiatry
No it doesn’t harm nervous tissue.
However….
The neural network is plastic, meaning that it can change. The connections between neurons can get stronger or weaker.
This is how nervous tissue learns. The connections are structurally plastic. New connections can form, redundant connections wither.
Obviously there are processes to make sure the network wires up correctly.
Now part of that control is through endocannabinoid transmission. Endocannabinoids are involved
in new learning in the network. When people take cannabis, learning is impaired. The exogenous cannabinoid
overwhelms the endogenous cannabinoid system. Cannabis impacts upon plasticity in the network.
With repeated use there will
be subtle changes in the network. This is at a level which is too fine grained for any scanning technology. But actually
it is is irrelevant even if researchers report a difference in brain volume, either slight increases here or decreases there. It is not
damage or harm. If one practises a musical instrument and becomes very proficient, the musical cortex expands slightly
as the connections become richer.
So overall, cannabis effects brain plasticity. It is not damage per se. However, the networks can become skewed
from their prior trajectory. Some users become trapped in nothing but cannabis, and laze around, not really achieving much.
And of course sometimes the networks are pushed into a state which resembles major mental illness. In that sense, cannabis can be a cause of much suffering.
Does marijuana harm the brain?
Emmanuel Onaivi has answered Unlikely
An expert from William Paterson University in Molecular Biology
The quick answer is NO. Please note that there is no medicine or substance without side effects. However, marijuana is a very safe drug. The human body makes its own natural marijuana compounds that are called endocannabinoids. The receptors activated by marijuana use are encoded in our genes on chromosome 1 and 6. There is a huge new knowledge indicating that marijuana system in the human body and brain plays important roles in reproduction and growth.
Have a question about science, health, fitness, or diet? Get cited, evidence-based insights: Consensus is an AI-Powered Academic Search Engine.
Try for free