As these studies were conducted in different variety of animal models involving different experimental setup, cannabinoid molecules, and their respective doses, it is difficult to draw any conclusion (Richter et al., 2018). Over the next decade, the National Institutes of Health is funding the Adolescent Brain Cognitive Development (ABCD) study—a major longitudinal study that will track a large sample of young Americans from late childhood (before first use of drugs) to early adulthood. The study will use neuroimaging and other advanced tools to clarify precisely how and to what extent marijuana and other substances, alone and in combination, affect adolescent brain development. The CB1 receptors in the ECS are found on many brain cells, including astrocytes. Astrocytes play multiple positive roles, including maintaining the blood-brain barrier, providing nutrients to neurons, and regulating neurotransmitter function. Another study demonstrated that CB2 receptor plays a major role in driving neuroblast migrations as well as subsequent neurogenesis in the peri-infarct cortex after experimental stroke in mice which positively impact stroke outcome.
However, additional and more specific studies will be necessary to determine their relevant contribution to the onset of cerebrovascular and neurological disorders. Interestingly, all the cannabis users do not experience cognitive impairment which clearly suggests the impact of genetic vulnerability on detrimental effects of cannabis (Blanco et al., 2016; Levine et al., 2017; Hasin, 2018). A recent study reported that genetic predisposition and THC exposure synergistically activates the NF-κB-COX-2 signal in astrocytes. This activation results in excessive glutamate secretion and decreased immunoreactivity of parvalbumin-positive presynaptic boutons around pyramidal neurons of the CA3 area of the hippocampus as well as impaired memory.
Inside the secretive cannabis lab that makes futuristic weed
Those who used marijuana had an average reduction of 4 IQ points by early adulthood. Please note that the studies covered in this article mainly consider the effects of tetrahydrocannabinol (THC) on the brain. THC is the psychoactive compound in marijuana, or cannabis, that creates the ‘high’ effect. The authors found that current users of marijuana performed worse on tests of verbal memory and processing speed. Yet other studies — including this 2015 study — report no significant differences between the brain shape and volume of daily marijuana users and non-users.
Many researchers believe that weed does take a toll on those who start heavily consuming weed in adolescence.6 But more research purports the positive effects that weed can have on adults. Through ongoing research, scientific understanding of cannabis and its effects on the brain is continually evolving. Stay updated with the latest how long does a hangover last plus how to cure a hangover fast findings and consult your healthcare professionals to make informed decisions. Whether you are considering or currently using medical marijuana, following these suggestions can help you achieve your best experience. Remember these guidelines to ensure your cannabis use remains beneficial without compromising brain health.
Although CB1 receptors are scattered all over the body, these are present predominantly in anatomical regions of the brain (Grotenhermen, 2005) related to memory, anxiety, cognition, pain sensory, motor coordination, endocrine function (Herkenham et al., 1990; Adams and Martin, 1996). CB1 receptors have the inhibitory action on cAMP production which is facilitated by the activation of adenyl cyclase inhibitor subunit of G proteins (Gi/0 proteins). Ultimately, this leads to an inhibition of N and P/Q type calcium currents and an activation of A type, inwardly rectifying potassium currents and mitogen activated protein kinase (Sierra et al., 2015) (see Figure 3). In 2015, the National Institutes of Health (NIH) began the Adolescent Brain Cognitive Development (ABCD) study that aims to understand how tobacco, alcohol, marijuana, and other drug use impacts adolescent health and brain development.
Effect of Cannabis Inhalation on the Cerebrovascular System
Some of these controversial results could be attributed to the length of exposure such as acute vs. long term chronic exposure. As for the overall pro-oxidative effect of smoking marijuana, it is very likely that ROS are generated as a byproduct of combustion rather than a direct effect of cannabinoids. Similarly to tobacco smoke where most of the oxidative stress is generated by the combustion of tobacco rather than exposure to nicotine which can also promotes OS but to a much lower extent (Naik et al., 2014). From these studies we can conclude that among the 107 neurovascular cases, almost 84% were ischemic stroke related to cannabis or cannabinoid use (both natural and synthetic). Considering Table 1 it is found that, young population is experiencing alarming number of neurovascular complications due to recreational use of cannabis.
- This because many studies track small samples of people over short periods.
- CB receptors mainly belong to the G-protein coupled receptor (GPCR) family, having inhibitory function on the cyclic adenosine monophosphate (cAMP) pathway through intracellular signal transduction (Richter et al., 2018).
- From studies in isolated cerebral vessel of rabbit and cat, it has been found that cannabinoid mediated vasodilation through CB1 receptor by inhibiting Ca+ influx in cerebral arterial muscle cell as well as possibly through arachidonic acid metabolism (Ellis et al., 1995; Gebremedhin et al., 1999).
- “Our understanding of the effects of marijuana on the brain is imperfect, and human research in this area is a work in progress,” said Dr. Fernando D. Testai, neurologist and professor at the University of Illinois at Chicago, in a news release.
It transports essential nutrients which are required for the normal metabolism of the brain cells (Sivandzade and Cucullo, 2018). The BBB is primarily composed of endothelial cells, pericytes, and astrocytes restricting the communication between blood and the brain parenchyma (Abbott et al., 2010). As a result, the BBB plays a pivotal role in restraining the entry alcohol poisoning of neurotoxic plasma components, xenobiotics, blood cells, and pathogens in the brain (Winkler et al., 2011) thus protecting the CNS from inflammation, injury, and different types of diseases (Daneman and Prat, 2015). On contrary, the BBB also limits drug delivery into the brain to treat different neurological diseases (Abbott, 2013; Kaisar et al., 2017).
Due to extensive lipid solubility and large volume of distribution, THC has a long biological half-life (18 h to 4 days) (Adams and Martin, 1996; Ashton, 2001) and gets distributed in adipose tissue, liver, lung, and spleen (Chiarotti and Costamagna, 2000; Sharma et al., 2012). Hydroxylation of THC generates psychoactive compound, 11-hydroxy ▵9_tetra hydrocannabinol (11-OH-THC), and further oxidation of this compound yields inactive compound, 11-nor-9-carboxy-▵9-tetrahydrocannbinol (THCCOOH) which is important for diagnostic purposes (Musshoff and Madea, 2006). The bioavailability of ▵9 THC depends on several factors including inhalation depth, duration of puff, and breath hold. It has been found that, the systemic bioavailability of THC is around 23–27% in heavy users whereas the value is 10–14% in case of occasional users (Sharma et al., 2012). The time to reach maximum plasma concentrations for ▵9 THC, 11-OH-THC, and THCCOOH is 8, 15, and 81 min after onset of smoking, respectively. On the other hand, systemic absorption of THC is relatively slow after oral ingestion compared to inhalation.
These detrimental effects of cannabinoid may vary from person to person because of genetic variability. For instance, the exposure of adolescents to cannabinoids leads to severe memory impairment compared to adult (Jouroukhin et al., 2019). Additionally, fatal brain development can also be affected by cannabis exposure during pregnancy which may ultimately result in impaired vision and coordination, larger intermittent attention, as well as behavioral problems in children at later phase (Wu et al., 2011). Schematic illustration of the Activation of the cellular antioxidative response system under normal and stress condition. Under normal conditions, the response to injury is adaptive, designed to restore homoeostasis and to protect the cell from further injury.
It was also suggested that, endocannabinoid tone is essential for this process by promoting migration of neuroblasts toward the injured brain tissue which leads to increased number of new cortical neurons. As a result, motor functional recovery is increased which is beneficial for improving the outcome of aged patients as well as reducing their disabilities after chronic stroke (Bravo-Ferrer et al., 2017). The result from these large sample size studies provide information on the temporal relationship between cannabis use and cerebrovascular complications like intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and ischemic strokes (IS). Along with cannabinoids, other predominant risk factors were also considered in the assessments however, these studies have several limitations. This include lack of consideration for the high lipid solubility of cannabis metabolites which helps them to persist in fatty tissues, therefore they may be detected in the urine weeks after the initial use (Mateo et al., 2005) and this may lead to erroneous result interpretation.
Long-Term Effects of Marijuana Use
CB2 receptors are primary located in spleen, skin, and bones as well as the immune cells. However, long-term marijuana may increase a person’s risk of substance use disorders, as well as problems with memory and concentration. Gray matter refers to regions of brain tissue that contain nerve cell bodies.
Although cannabinoid-based drugs have shown some therapeutic activities against neurological and psychiatric disorders the effect of cannabis on the neurological system cannot be denied. It has been demonstrated from various in vivo studies that THC is responsible for inducing dose-dependent toxicity as well as causing structural changes in those parts of brain which are rich in CB1 receptors. These receptors are located primarily in cerebellum, hippocampus, amygdala, prefrontal addiction and recovery cortex, and striatum (Lawston et al., 2000; Downer et al., 2001; Burns et al., 2007). This disconnect between in vivo and human studies might be due to the different sample characteristics, inter-individual variabilities related to past history of drug use, consumption rate, psychological problems, and differences in the experimental methodology (Batalla et al., 2013). These regions of the brain control motivation, emotion, and affective processing (Battistella et al., 2014).
Although the mechanism behind THC induced cognitive and behavioral dysfunction is yet to be established, recent studies conducted on mice model have demonstrated that these detrimental effects are facilitated by astrocyte CNR1 (Han et al., 2012; Chen et al., 2013). Moreover, THC may activate nuclear factor κB signal as well as upregulate cyclooxygenase-2 (COX-2) which may result in elevated release of glutamate by astrocytes (Bezzi et al., 1998). Interestingly, it can also be noted from these case reports that the occurrence of neurovascular diseases such as stroke has drastically increased after 2010. Widespread availability of cannabis or synthetic cannabinoids and its legalization across the world may be the underlying reasons behind this.
That’s why you might have trouble remembering if you smoke weed or eat a THC-infused edible. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. LC assisted with the drafting of the manuscript and preparation of the figures. People who drink, smoke cigarettes, or use marijuana from a young age are also more likely to do so later on in life. More studies need to be done to understand if this effect also applies to humans.
While researchers do not always agree (and likely never will) about every medical aspect of cannabis, the consensus leans towards cannabis being safe for consumption when used in appropriate doses by people of appropriate ages, but further research is needed. Available research offers some insight into the short-term effects of drug use. However, it is difficult to draw definitive conclusions regarding the long-term effects of drug use. This because many studies track small samples of people over short periods. The researchers found that the rats they exposed to cannabinoids had a significantly better working memory in adulthood than the control rats.
What are the long-term effects of marijuana on the brain?
Moreover, compilation of these case reports indicates that along with cannabis or cannabinoids use, other risk factors like alcohol, tobacco, dyslipidemia, migraine without aura, hypertension etc. also act as prodromal factors for the onset of cerebrovascular diseases. Apart from being used as a medicine, cannabis or marijuana is the most widely abused recreational drug all over the world. The legalization and decriminalization of cannabis in Canada and various states of USA may be the underlying reason of the widespread popularity of it among young population. Various studies have reported about the relationship between cannabis use and different detrimental effects like cardiovascular, cerebrovascular, and neurological complications among different age groups.
