Motivation and emotion/Book/2022/Cannabis use and dopamine

Overview


Dopamine is a neurotransmitter which has many important functions in the brain; it is distributed via neuronal pathways in the brain. It is known as the feel-good neurotransmitter (see Figure 1) and, as a result, dopamine is associated with addiction. This is due to the neurotransmitter being linked with the reward system and approach-based motivation.

Cannabis is a drug that affects one's physiological and psychological state as well as inducing behavioural changes. It can be prescribed medically or used recreationally. Cannabis is mostly illegal around the world; however it is decriminalised and even legal in some places (For example, in the Australian Capital Territory [ACT] it is decrimialised ).

Cannabis can have a negative effect on the brain's dopamine system. This poses a problem as excess cannabis use can be detrimental for both a developing and developed brain, due to the many roles dopamine modulates for. Excess cannabis use can cause problems for motivational behaviour and have adverse effects on an individual's mental health in the long run. This book chapter addresses 3 key focus questions about the impact of cannabis on dopamine in the brain.

Focus questions:
 * What is the impact of cannabis use on dopamine in the brain?
 * What complications may this cause?
 * How can cannabis be managed?

Brief history of cannabis
Cannabis is a psychoactive drug which is harvested from the Cannabis plant. Cannabis the drug, is also known as marijuana, weed amongst other names, whereas the flower itself is known as bud.

Use


Cannabis can be used both recreationally and medically and can be smoked, vapourised or consumed (edibles) in order to achieve the desired 'high'. Recreationally speaking all three methods are popular, yet it is predominantly smoked for medical use. A cannabis cigarette is known as a joint (figure 2).


 * 1) Recreational
 * 2) Medical

Effects
There are a wide range of effects which cannabis can induce concerning both physiological and psychological effects. While some effects are desirable others are neither desired nor enjoyed by recreational users. In extreme cases cannabis can cause psychosis especially in long-term users. Most common effects include:

Physiological:


 * Cottonmouth (Dry mouth)
 * Bloodshot eyes
 * Relaxed muscles
 * Increased appetite (also known as the munchies)

Psychological:


 * Euphoria
 * Anxiety
 * Hunger
 * Relaxation

Dopamine
Dopamine is a neurotransmitter which is manufactured in the ventral tegmental area and ultimately processed by the nucleus accumbens to produce the feeling of pleasure. These brain areas, paired with the ventral striatum make up the brain's mesolimbic pathway, which is also known as the reward pathway. As a result, dopamine underlies addiction, as naturally, being linked with the reward system, it involves feelings of pleasures and rewards. In a behavioural sense, it can underlie gambling addictions, as pathological gamblers produce excess dopamine than casual or non-gamblers in the ventral striatum, with dopamine being in excess for near-misses, showing that dopamine motivates loss-aversion rather than motivation to chase a big win.

Dopamine is linked with motivation towards goal pursuit. This is because dopamine underlies the reward pathway. Montague et al., (2004) indicate that overstimulation of dopamine leads to engagement in compulsive and dangerous goal-directed behaviour. Moreover, Grace et al., (2007) highlighted that dopamine regulates for the balance in the limbic system, which concerns both limbic and frontal cortical information. This frontal cortical information comes from the prefrontal cortex, which is associated with planning, and goal setting (Spiers, 2008), thus, demonstrating that dopamine regulates for goal-directed behaviour.

Effects and outcomes of cannabis use on the dopamine system
Cannabis affects dopamine as THC (tetrahydrocannabinol), the psychoactive chemical that causes the "high", binds to endocannabinoid receptors in the brain and prevents the release of the inhibitory neurotransmitter Gamma-Aminobutyric Acid (GABA) in the ventral striatum (which is part of the reward system) and therefore, dopamine release is increased in nearby neurons. Due to GABA not being released, this constant release of dopamine causes the euphoric effects associated with cannabis (Bossong et al., 2008). This can affect our dopamine system as constant overfiring due to an inhibited refractory period can cause a drop in dopamine when sober. When comparing cannabis users with non-users it was found that there was a diminished dopamine synthesis capacity in a regular user's brain, especially the striatum and it's limbic subdivisions (Bloomberg et al., 2014). Yet, this study could not establish a link between the reduction of dopamine in these brain areas and symptoms of psychosis, similar to those displayed in schizophrenia. Therefore, these findings suggest that the modulations cannabis inflicts on the striatum cannot explain for cannabis-induced psychosis, and that it is most likely caused by other effects cannabis causes in the brain. Furthermore, studies have concluded that pregnant women using cannabis to treat morning sickness are inadvertently altering their children's endocannabinoid system (Brown et al., 2017; Agrawal et al., 2019), meaning the child's natural development of the central nervous system could be hindered. Baker et al., (2018) indicate that this is due to the transfer of THC into the breast milk that the children are ingesting. A review by Hurd et al., (2019) underpins the effects of cannabis use on developing brains in adolescents, stating that, the endocannabinoid system is at its peak activity and expression during adolescence, therefore putting teenagers at risk to fall victim to drug addiction. This is due to the endocannabinoid system being linked with the mesolimbic reward pathway (Hurd et al., 2014). So constantly stimulating this area can cause for a dependence on cannabis to attain the feel-good effects the mesolimbic pathway produces on an already high active endocannabinoid system. In addition, Hurd et al., review brain studies of cannabis users having had their brain neurologically imaged using fMRI (figure 3), PET etc. These studies revealed that cannabis users had higher activations in the right inferior pre-frontal gyrus and in the right putamen, which ultimately extended into the striatum and insula, than did non-users. These brain areas are impaired by disorders such as addiction and schizophrenia, suggesting that cannabis use in a developing brain can lead to a greater risk of developing an addiction and/or a psychological disorder.

Cannabis on motivation
Dopamine is associated with the mesolimbic pathway, or the reward pathway. When smoking cannabis, dopamine release is increased, which activates the mesolimbic pathway, and when Cannabis is frequently ingested this reward system is activated more frequently than natural. This constant overstimulating of this pathway may have negative effects for cannabis users. A review by Hall (2014) into the effects of cannabis use found that cannabis use before the age of 15 may cause incompletion of school (dropout) or choosing not to transition into higher education. However, these findings are unclear on whether cannabis is in fact the sole cause for school dropout, with studies reviewed stating it could be due to a mix of genetics and environments too.

Another review found evidence that cannabis use can actually cause amotivational states in individuals (Volkow et al., 2016). This was concluded by a fair amount of studies, however, many of which were conducted more than 15 years ago, with the more recent ones being from 2014. Despite this, a study reviewed present findings which indicate that cannabis use can cause for reduced motivation for reward-associated behaviour, such as learning. Meanwhile, neuroimaging of the ventral striatum showed that cannabis users had a decreased reactivity to dopamine stimulation, which could contribute to negative emotionality, and a reduced engagement in activities that were not drug related. This could be due to the act of smoking and getting high taking priority over other activities such as learning, leading to a skewed reward hierarchy. A more recent review of cannabis use and motivation was done by Pacheco-Colón et al., (2019). This review builds upon Volkow et al., (2016), while also concluding that the reason cannabis may cause for a reduction in motivation is due to long-term cannabis use causing depression or depressive symptoms, resulting in these amotivational states. The review states that there are sufficient studies that provide evidence that cannabis may cause depression. Although, it may not be as clear-cut as that, as some studies state that individuals may be self-medicating for their depressive symptoms. This implies that cannabis may not always lead to depression, especially as depressed individuals may also be susceptible to abusing other substances.

Potential complications of long-term cannabis use
Prolonged cannabis use can be problematic due to how it influences the brain and its neurological pathways. Psychosis is a psychological disorder in which an individual's sense of reality is seriously warped. The National Institute of Mental Health states that when an individual has a psychotic episode, they may have difficulties in understanding what is real and what isn't. Many studies and reviews have been done to fully understand the relationship between cannabis and psychosis. One such review was done by Hasan et al., (2019) in which they determined that psychosis is more frequent in cannabis users; moreover, users can develop psychosis earlier in life than non-users. Hasan et al., also state that the risk of developing psychosis via cannabis use is dose-dependent and that cannabis users are more likely to relapse and have more severe symptoms. This review concludes that long-term cannabis use can indeed, cause for the development of psychosis by reviewing prior scientific literature from 2005-2016; however, it could not answer how cannabis may cause psychosis in a biological sense. Tost et al., (2010) suggest that dysregulation of dopamine can cause for psychotic symptoms. Patients show an excess production of dopamine in the striatum when stimulated by amphetamines. While this may not be cannabis induced, it can be seen that a surplus of dopamine in the brain can lead to psychotic symptoms.

Long-term cannabis use can cause other problems for individuals, as Hall's review (2014) also found that chronic cannabis use can cause cognitive impairments in individuals. Studies which investigated the impairments cannabis may cause found a deficiency in verbal learning, attention, and memory. One study measured cognitive functions beforehand and compared results after cannabis use (Block et al., 2002). These cognitive impairments and their severity are dependent on the dosage and frequency of use. Solowij (2002) found a partial recovery from the impairments by abstaining for at least 2 years. Yet, informational processing was still impaired. A more contemporary review by Kroon et al., (2021) is in concordance with Hall (2014), presenting that cannabis can cause for impairments in learning and recollection. However, the researchers suggest that the long-term effects of cannabis are less conclusive than the effects of acute cannabis use, and are therefore open to interpretation. This may be due to difficulties in creating a solid methodology for measuring the long-term effects of cannabis use, due to individual differences in cognition and history of cannabis abuse.

Theory behind the motivation of cannabis use
Pinpointing the most appropriate theoretical models and frameworks into the motivation to use cannabis is difficult. The most applicable theory is the Theory of Planned Behaviour (TPB) (figure 4). The TPB was proposed by Azjen, (1985). The theory of planned behaviour is comprised of three facets: Attitudes, Subjective Norms and, Perceived Behavioural Control. The aim of the theory is to explain behaviours by the intentions behind them. Attitudes towards a behaviour are based upon the individual's beliefs about the outcome from performing said behaviour and whether it will produce its desired outcome. This, along with subjective norms from society about the behaviour (motivating one to fit in) and the perceived behavioural control over the behaviour interact to predict the engagement of behaviour. It builds upon the Theory of Reasoned Action.

Conner & McMillan, (1999) demonstrated that TPB can predict for cannabis use. It was found that attitudes towards cannabis, injunctive norms (what one ought to do) and perceived behavioural control predict for intentions of use. Actual cannabis use was predicted by intentions.

Research conducted by Ito et al., (2015) applies the TPB toward cannabis use in the US. The researchers used a longitudinal study method (over 3 years) in which participants were interviewed on their marijuana use in the prior 30 days of the interview. The participants also completed self-report measures on their attitudes to using cannabis. The study demonstrated that those who used cannabis frequently displayed positive attitudes toward cannabis, high intentions to use cannabis and to be in the proximity of those using it, with less-confident ability in rejecting marijuana use. Overall, the study found that injunctive norms and attitudes predicted both intentions to use cannabis and cannabis use a year later, whereas descriptive norms (characterisations of behaviour that are seen as typical, i.e. how people actually behave) did not predict for intention of marijuana use. Growing intentions to use marijuana predicted a greater use of it a year later. This study shows that intentions for use and how they grow over time is the best predictor for actual cannabis use, which are rationalised by injunctive norms. This study is in concordance with Conner & McMillan (1999).

Moreover, Gomis et al., (2018) investigated the intentions to use cannabis in 4 European countries, using the Cannabis Use Intentions Questionnaire (CUIQ) (Lloret et al., 2018). Self-efficacy to abstain from cannabis use was negatively linked with actual cannabis use, meaning the lower one's self-efficacy, the more likely to use marijuana. Also, subjective norms were the lowest predictor for cannabis use, which the researchers comment is in line with prior studies (McMillan and Conner, 2002). Cannabis use intentions were the best predictor for actual use. Meaning that, in this study intentions to smoke cannabis aren't really influenced by societal beliefs about the behaviour.

These studies show that intentions to use cannabis and attitudes towards the drug were the best predictors for actual cannabis use, while intentions were rationalised by injunctive norms. Obviously, lower self-efficacy to abstain predicted for higher cannabis use. These findings highlight the cognitive factors which influence cannabis use, which is helpful as methods to reduce and prevent cannabis use can be concluded from these findings.

Legality of cannabis
It is illegal to cultivate, sell and possess cannabis in most states and territories in Australia. However, in the ACT (figure 5), it is decriminalised. Individuals over the age of 18 are allowed to have up to 50 grams of dried cannabis and up to 150 grams of fresh cannabis. Furthermore, individuals can grow up to 2 plants per person, with a maximum of 4 plants in a household. Despite this, it is still illegal to sell cannabis and drive under the influence of cannabis. This law was passed on the 31 January 2020.

The status of cannabis within the world differs from country to country, with medical and recreational use differing too. With the majority of countries deeming cannabis to be illegal, with some countries in Asia and the Middle East seriously apprehending offenders with severe sentences. Despite this, countries such as Canada, Mexico Thailand, and Uruguay, to name a few. With the commercial sale of cannabis being legal in Canada (figure 5), Thailand, Uruguay In the US, 19 states and 2 territories as well as the District of Columbia (Washington DC) also legalised the recreational use of cannabis. In 2020, a rescheduling law was passed which classified cannabis as a Schedule 1 drug, meaning that those countries whom signed the treaty, can medically prescribe cannabis to their respective populations.

Shift in attitudes of cannabis
A review into the attitudes toward cannabis was done by Carliner et al., (2017) in the US. The data they reviewed comes from public records and scholarly articles. In addition, Carliner et al., give a brief history of cultural attitudes toward cannabis. In the early 1900s cannabis was seen as a dangerous drug, with a journal article in 1936 stating that individuals who were intoxicated would "suddenly turn with murderous violence with knife, axe or gun". In the 1960s and '70s, there was a increase in use amongst white young adults which caused for an increase of arrests in California, which was expensive for the state government. Thus, the First Lady at the time (Nancy Reagan) endorsed "Just say No", a campaign against the widespread and mainstream use of cannabis. The review goes on to explain that attitudes have become more accepting, and that in 2011, there was a national high for favouring opinions over recreational cannabis, since being nationally tracked in polling since the 1970s. . Carliner et al., conclude that cannbis use has increased since 2002, and that attitudes toward cannabis are shifting in a more positive and accepting light. Also that the preference of medical marijuana treatments are increasing amongst the American population. Furthermore, adults and adolescents no longer view cannabis usage as a big risk for harm, despite cannabis use having many adverse effects. When medical marijuana laws were passed, studies could not establish a causal relationship between the passing of these laws and cannabis use patterns amongts adults and adolescents. So, the researchers suggest to investigate how legalisation laws can influence the usage of cannabis for adults and adolescents and the implications this may cause.

Cannabis culture
Since there has been a contemporary shift in attitudes toward the status and use of cannabis, especially in the US, there has been a growing subculture of cannabis users and advocates. People who partake in frequent cannabis use are known as "stoners". With this growing subculture, festivals and celebrations of cannabis have also grown in popularity and infamy within pop culture. By far, the most well-known and popular festival is known as 420 (or 4/20, 4:20, and pronounced four-twenty), in which users gather in parks or public spaces to smoke cannabis, or whichever method of ingestion they prefer, and spend the day together (figure 6). The "festival" is celebrated on the 20th of April as it is 4/20 in the US date format. Skliamis & Korf (2019), state that cannabis festivals represent the growing positive attitudes and contemporary push for legalisation in modern times. The researchers also indicate that while characteristics of celebrations may be similar, the underlying motivations and customs and attitudes are still culturally specific to the country it's being held in.

Quiz
Quiz {Cannabis inhibits the production of GABA: + True - False
 * type="(True)"}

{Cannabis causes high motivation in individuals: - True + False
 * type="(False)"}

Conclusion
This chapter discusses the effects and implications of cannabis use on dopamine in the human brain. Cannabis inhibits the release of GABA in the ventral striatum, which in turn, causes dopamine to keep on firing in the brain. This accounts for the euphoric effects induced by cannabis, as dopamine is known as the "feel-good" neurotransmitter. Moreover, due to the ventral striatum being stimulated by cannabis, it can cause for addiction as this brain area correlates with rewards due to it being part of the mesolimbic pathway (reward system).

A variety of complications may arise from frequent and long-term cannabis use. This includes psychological disorders such as psychosis and depression and impairments in cognitive functions like memory, attention and learning. In addition, motivation is affected by long-term cannabis use as goal-directed behaviour is affected, such as the motivation to learn.

Applying the Theory of Planned Behaviour toward cannabis use can explain for the reasons why individuals engage in the behaviour and how cannabis use can be reduced or controlled. First, intentions to use cannabis were predicted by attitudes towards it, perceived behavioural control of use, and injunctive norms. Meanwhile, engaging in the actual behaviour of using cannabis was predicted by the intentions to use it. As a result, methods to reduce cannabis use can be identified by evaluating how attitudes are formed over cannabis use. Alternatively, methods into controlling cannabis use can be considered instead. With a couple of countries moving toward decriminalisation or even nation-wide legalisation of cannabis, modelling this can allow for state-controlled distribution of cannabis, similar to how alcohol is distributed within a country.