Marijuana and the brain

Marijuana is the most widely used illicit drug in the United States in the adolescent population, and almost half (44%) of senior high-school students have reported using marijuana in their lifetime . Of these, 5% report daily usage; which seems to decrease with age . In Lebanon the drug is used by just 4.6% of the population of the Beirut metropolitan area during their lifetime. Studies pertaining to the beliefs held by drug users and the public at large concerning the harmfulness of drugs of abuse have revealed disturbing misconceptions. This includes the finding that ratings of perceived harmfulness seem to decrease not only for the drug being abused, but also for other drugs as drug usage increases . This finding is particularly alarming, and it aids in illuminating the complexities involved in rehabilitation and in treatments for drug addiction. Despite cognitive, social as well as neurological evidence to the contrary, the existence of marijuana addiction and conversely marijuana dependency has been disputed and it is not as of yet included as an addictive disorder in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Nevertheless, treatment options have been made available for the rehabilitation of individuals experiencing marijuana addiction and some have shown to be successful. The effects of marijuana usage are widespread, and can be examined from a variety of different perspectives. It’s adverse effects impact users on a cognitive, social as well as neuroanatomical level. In the cognitive domain, chronic marijuana use has been linked to impairments in memory, attention, learning ability as well as in motor coordination. Many adolescents become exposed to marijuana in social settings, and as such the social context of marijuana use plays a significant role in its use by interacting with neuroanatomical factors. Chronic use of this substance may lead to physical changes in the brain, which may affect the behaviour of the individual and their interactions with the environment.
Cognitive Correlates of Marijuana
Brain Function and Adolescent Marijuana Use
Previous studies have attempted to examine the effects of marijuana usage on the brain using functional imaging methods. Functional imaging is a relatively new technique that measures the oxygen consumption of cells in the brain and transfers this into an image; cells that are more active use more oxygen. Functional magnetic resonance imaging (fMRI) has been used in a number of studies to observe patterns of brain activity in relation to cannabis use. These methods have shown evidence that heavy marijuana users have a reorganization of neural networks in relation to spatial working memory demands . Adolescent marijuana users showed increased activation in the right parietal lobe and increased activation in the right dorsolateral prefrontal cortex. have been shown in marijuana users. This suggests that adolescents are especially susceptible to the long-term adverse effects of marijuana usage; a finding that is especially troubling considering that marijuana is most widely used by adolescents. Furthermore, fMRI studies have shown an increase in spatial working memory in brain response in marijuana users compared to non-users . A study conducted by Lane et al. in 2005 demonstrated that marijuana users exhibited significantly reduced motivation than non-users. In a study where participants were instructed to gain as much money as possible via two possible ways, marijuana users switched over to the method which required less work and effort sooner than non-marijuana users . The learning experienced from using marijuana multiple times suggests that memory may play a part in the use of marijuana, and it's not surprising that drug reinforcement and addiction has been examined from expectancy and memory association perspectives. In these paradigms, expectancy is viewed as implicit nodes of information pertaining to marijuana that is connected to an extensive semantic network that joins the individual’s prior experiences (and therefore memories of these experiences) that are in some way related to the idea of marijuana. These expectancies act as associations that bind memories, and the more memories an individual has that are related to a specific idea, the more probable it is that this network will be activated. This network can be activated by a variety of stimuli that are captured by a variety of senses and subsequently encoded into memory, and is thus cross modal . For instance, a particular smell may elicit a visual memory, or a particular sound heard by the individual may elicit a specific smell from memory. These memories also extend to affective evaluations as well as motor sequences associated with a particular experience. As a result, stimuli encountered in the environment may activate this network and thus influence the individual’s resulting behaviour. Using this paradigm as a framework for research, studies have found that marijuana users are more likely than non-users to activate this network when presented with cues related to marijuana usage (i.e. marijuana paraphernalia) in comparison to neutral cues. Furthermore, heavy users’ networks consist of positive expectancies such as relaxation, enhanced abilities on cognitive tasks, as well as stimulating social behaviour, whereas the opposite effect was found in non-users. This may help explain the reinforcing effects of drugs on individuals who as a result become addicted to the substance. As such, it becomes difficult when attempting to disentangle the chemical effects of marijuana from the associations between previous experiences, since both play a part in addiction. This becomes especially apparent in the phenomenon known as reverse tolerance, in which individual differences result in different experiences when initially exposed to marijuana. Some individuals fail to experience the intoxicating effects associated with marijuana usage during primary exposure, and these effects materialize only after multiple exposures . Drug users attribute more positive connections to drug use than non-users, and as such they become biased in their evaluations of related as well as unrelated cues and are more likely to connect neutral cues to the drug network than non-users . Furthermore, when presenting these cues to marijuana users, they are more likely to report cravings for the drug .
Motor Skills
Not only are the motor skills of adults and adolescents affected by the effects of marijuana but children and newborns born to cannabis users also suffer from such motor problems. Newborns and infants born to cannabis users have increased tremors, exaggerated startle responses and poor habituation to novel stimuli and by the age of 10 children were reported to have increased hyperactivity, inattention, and impulsive symptoms .
Within adolescents and adults results from investigations using positron emission tomography (PET) and fMRI techniques have reported metabolic alterations within frontal regions of marijuana smokers . These areas are involved in skills and judgement tasks and the effects of marijuana on these areas result in decreased capacity to accurately judge distances, slower reflexes and distorted perceptions . In addition, as mentioned previously, psychomotor functioning is affected while under the influence of cannabis; this lends another explanation to impairments in driving ability.
For occasional or recreational users, substantial results have not been found to support the claim that driving is also impaired for these users. This is not to say that occasional users do not exhibit deficits in driving. They do exhibit impairments in driving stimulations; however, these are more modest impairments .
Adolescents, as a demographic, are prone to making many risky decisions. These decisions, unfortunately, often have adverse and/or immediate consequences on their health and well-being. According to the cognitive model of drug addiction proposed by Beck, Wright, Newman, and Liese (1993) , there are three core drug-related beliefs associated with drug dependence: 1) liberal beliefs, where drug use is considered acceptable and normal; 2) anticipatory beliefs, where positive consequences of drug use are expected; and 3) relief-oriented goals, where the drug is used to relieve stress or to provide an escape.
A study conducted by Chabrol, Massot, and Mullet (2004) investigated which of the above three beliefs predicted cannabis use among adolescents. Surveys which assessed participants’ drug use beliefs were distributed to a sample of high school students. Results showed that liberal beliefs were found to be associated with cannabis use, while relief-oriented goals predicted cannabis dependence among heavy users . The study’s authors have stated the clear implications of these findings, indicating that treatment for heavy marijuana users should target these two specific beliefs.
Longitudinal studies
A longitudinal study was conducted, which followed a sample of marijuana dependent adolescents into adulthood. Heavy marijuana use continues to have a lasting effect for approximately 25 years, thereby continuing into middle adulthood Results demonstrated gender differences in socioeconomic status and employment in adulthood. Females who were heavy users in adolescence were at a greater risk of experiencing poverty, having a lower income at 42 years old, and having a period of unemployment between ages 32 and 42 years . A related study found similar results, where the level of education obtained by a heavy user was lowered compared to nonusers or light users . Synaptic contacts connect neurons (nerve cells in the brain) by enabling them to communicate with each other, and if these contacts are disturbed, the area will not be able to function properly. Furthermore, it seems as though depressive mood states in females are initiated by chronic THC administration to adolescent rats, thus indicating morphological changes in the emotional circuit in the brain. Lasting deficits in recognition memory were also found in adult rats that had been chronically treated with THC in adolescence, and short-term learning impairments were also found. Adult rats who are administered THC in adulthood do not show any of these long-term effects, thus providing evidence that adolescents are especially vulnerable to these adverse effects produced by THC. These changes have been objectively measured by counting the amount of presynaptic (before the synapse) and postsynaptic proteins (after the synapse) VAMP2 and PSD95, respectively, in the hippocampus. Complex brain functions (such as learning and memory) require new synaptic contacts to be made, and decreases in VAMP2 and PSD95 can be found in adolescent rats treated with THC, thus indicating less synaptic contacts during these processes
There are also certain characteristics that have been found to be associated with chronic or daily cannabis users. These types of users are more likely to be male, to be less educated, to use alcohol and tobacco regularly, and to use a variety of other drugs such as amphetamines, hallucinogens, psychostimulants, sedatives, and opioids Additionally, many individuals—especially marijuana users—have the misconception that marijuana is a harmless drug with little or no negative consequences . Sociological risk factors associated with the initiation of adolescent marijuana use includes substance abuse by parents and friends, their attitudes towards substance use, and the number of friends who use marijuana . While parental factors, such as having dinner with parents, did not demonstrate the expected protective effect on adolescent substance use, it was found that school-related factors provided a greater protective effect on adolescent marijuana use. Specifically, talking to teachers about problems and being happy in school were found to be protective factors against adolescent marijuana use These receptors are for the most part pre-synaptic in location, and exert their effects by inhibiting the release of neurotransmitters. There are certain antagonists of this receptor, such as rimonabant, that are able to block the activation of the cannabinoid receptor. These antagonists could serve as a contemporary means for treating drug addiction since they prevent drugs from accessing the brain, which in turn would extinguish the rewarding effects associated with these substances . It is assumed that these findings can be generalized to humans, so it is clear to see the possible implications that this may pose socially. The hippocampus is critically involved in memory processes and the cerebellum and basal ganglia play a role in movement; which suggests an involvement of cannabinoids in short-term memory interference and inhibition of movement . Individual differences have been found with respect to cannabanoid tolerance. This can be explained on a cellular level, where different people display varying concentrations of CB1 receptors in different locations in the brain. Repeated administration of high doses of cannabinoids or chronic administration of smaller doses of cannabinoids leads to tolerance in the form of the downregulation and desensitization of receptors; which has recently been found in the brains of human cannabis users. This adaptive mechanism varies by brain region, where some regions exhibit greater tolerance in comparison to other regions <ref nameBerrendero2006/><ref nameCassidy2008/>.
Tetrahydrocannabinol and Anxiety
Recent studies using animal models have shown that tetrahydrocannabinol may play a role in inducing anxiety-like behaviour in rats. This had been demonstrated using the elevated plus maze (EPM), which is a method used to determine the relative anxiety experienced by rats by observing how much time they spent in an enclosed arm of the maze versus an open arm of the maze. However, the specific role of cannabinoids in anxiety is controversial. Previous studies have found mixed results, where certain doses of cannabinoids produce anxiolytic-like response whereas others seem to produce anxiogenic-like responses, thus suggesting a dose-dependent behavioural response <ref nameBraida2007/>. Interestingly, these effects were also mediated by contextual factors in the environment, thus reinforcing the notion that internal and external variables interact to produce the organism’s experience. These studies have also used cFos expression to map anatomical regions and identify cells belonging to specific neurological circuits as they are activated to specific chemical as well as environmental stimuli. This helps researchers to identify the regions in the brain that are involved in certain responses to drugs of abuse. Evidence supporting this comes from the use of CB1 receptor antagonists, which when administered block and reverse the anxiolytic effects of THC <ref nameBraida2007/>.

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