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Motivation and emotion/Book/2016/Cannabis and negative emotions

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Cannabis and negative emotions:
What is the effect of cannabis on negative emotions?


Overview

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Case study

Jim is a 21 year old man who smoked cannabis socially throughout his teenage life. Jim had always felt good when he smoked cannabis, however he started to feel anxious and depressed. Jim thought that the most logical thing to do was to smoke cannabis in order to combat these emotions. As he began to smoke heavily, his motivation to work, enjoy recreational activities with his friends and maintain a routine diminished. Jim relies on cannabis to relieve his anxieties about getting his life on track but has noticed that he doesn't feel the same while high any more. He has become depressed, anxious, and paranoid. Jim wants to quit but knows about how hard it is to go through the withdrawal process to detox. Jim also realises that he has become dependent on the drug and wants to quit, however the dependency and addiction is too strong. Jim's loved ones are not sure where to turn but hope to find an effective psychological intervention to help with his addiction.

"Marijuana use can be associated with anxiety and other negative states. People feel bad, they use, and they might momentarily feel better, but then they feel worse. They don't necessarily link feeling bad after using with the use itself, so it can become a vicious circle." - Lydia A. Shrier M.D.

Figure 1. Cannabis leaf

Cannabis use to relieve negative emotions and induce feelings of euphoria and bliss can then not serves as a strong motivation to re-engage in cannabis use. Recent research[factual?] suggests an equally supportive argument for both the positive and negative effects of cannabis on human emotions especially in cases that involve cannabis use as treatment for anxiety and depression. However, as the drug has been legalised for medicinal use in America, more research has been conducted into the negative effects that cannabis has on individuals who use it long-term. One study found that 66% to 90% of cannabis users reported more[clarification needed] negative effects and a lower ability to empathise when tested on their ability to recognise emotions on faces varying from cheerful to angry (Gruber, Pope, Hudson et al., 2003).

While there is significant evidence to suggest that cannabis induces a calming effect on anxiety and panic like symptoms, some users still experience paranoia, panic attacks and psychosis symptoms while smoking pot[factual?]. So, if the majority of evidence suggests that cannabis has a calming and medicinal effect on emotional disorders like schizophrenia, anxiety disorders, and depression why do over half of users experience negative effects? And when using cannabis does not deliver the desired effect then ...

"What am I dong WRONG? Shouldn't cannabis relieve my anxiety/depression too?"

In short the answer is nothing and not necessarily. Cannabis is used for varying reasons and has equally varying results depending on a multitude of factors.

How the drug is used and the negative consequences based on these factors, both short- and long-term will be discussed in this article as well as the most prevalent psychological theory and research on the negative effects of cannabis use on emotion. The effect cannabis has on the emotional centre of our brain, the amygdala, will be discussed and the effect it has on the cause or exacerbation of mental illness will be examined. Furthermore, effective emotional and motivational based psychological theory integrated into intervention and therapy and its effectiveness will be discussed.

Cannabis

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Cannabis is a plant derived from Cannabis Sativa or Cannabis Indica (for varying effects of each type refer to Figure 2) and is made usable by drying the buds of the plant which can be ingested in a number of ways, including smoked via a joint or water pipe (bong) or eaten. Within the plants structure over 60 cannabanoids are present which provide the substance's psychoactive effects (McLaren & Mattick, 2010) on the user while the chemical tetrahydrocannabinol (THC) give the user a "high" sensation (Hall & Solowij, 1998).

Secondary to alcohol, cannabis the most widley used intoxicating substance in the world with a estimated 141 million (2.5%) of the world's population using it at least once in their lifetime (Green, Kavanagh & Young, 2003). In Australia it has been revealed that 16% of individuals who use cannabis, use it everyday and over half use it less than monthly (McLaren & Mattick, 2010).

In light of recent legalisation of cannabis for medicinal purposes in America, research has found that cannabis can have a positive effect on the treatment of chronic physical illnesses and help to alleviate anxiety and insomnia. However, there is conflicting evidence about the relationship between cannabis and negative emotions.

Brain physiology and the effect of cannabis

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Cannabis exposes the brain to large amount of chemical compounds found in the plant which includes cannibanoids such as tetrahydrocannabinol (THC). The chemical reaction in the brain is through the Endocannabinoid system endocannabinoid (EC) system. This system affects many parts of the brain including the cerebellum, cerebral cortex and nucleus accumbens. Which, in turn, affects the ability for the way in which the user feels, moves and reacts. The endocannabinoid system operates by communicating when the postsynaptic neuron is activated and cannabinoids are created from fat cells already in the neuron. Then they are released and travel back from the presynaptic neuron where they attach to cannabinoid receptors.

Cannabis and the amygdala

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During cannabis use THC overwhelms the EC system and the impairs the ability of natural neurons to communicate effectively. The main structure within the brain that has limbic-motor interface to regulate stress and anxiety is the amygdala and is central in our individual emotional processing[factual?]. When exposed to cannibanoids, the risk of experiencing negative emotions during and after use may increase[factual?]. A recent study investigating the natural ability of the EC system demonstrated the interaction between the EC system and THC alters stress responses and emotional learning[1]. This internal endocannabinoid system regulates anxiety by reducing the excitory signals used by neurotransmitters[2]. The effect of cannabinoids on this system involves the use of cannabis to relieve initial feelings of anxiety and stress short term, however long term use down regulates receptors which then leads to an increase in anxiety[3].

Long term cannabis users have shown a decreased reactivity to dopamine which may suggest a link to the inhibition of the reward system in the brain. This may cause an increase in negative emotionality and addiction severity [4].

Short- and long-term negative emotional effects

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The short=term effects of cannabis use usually manifest within seconds and take full effect within a few minutes lasting for around three to four hours depending on the individual and strain of the plant. Some short term negative effects include:

Short term

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Anxiety Between 20% to 30% of individuals have reported feelings of anxiety after use. Anxiety is the most commonly reported short-term side effect.
Panic attacks are another common side effect, however are more common after the individual hasn't engaged in use for a prolonged period of time.
Psychosis Usually lasts for around six hours. Episodes may be accompanied with aggression.[5]
Disassociation Use may result in short-term selective impairment of polysynaptic reflexes and can lead to states of depersonalisation and derealisation.[6]

The intensity and duration of the effect of cannabis has been shown to diminish after prolonged, chronic use as a tolerance to cannabinoids is increased. This creates a risk to the user as the short-term effects diminish, the more of the substance is used creating a cycle of addiction. Long-term users open themselves up to a much broader range of issues which affects their psychological and emotional well-being as well as their ability to maintain a healthy lifestyle. Some negative long-term effects of cannabis use include:

Long term

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Decreased mental capacity Cannabis has been linked to a decreased ability to process information quickly, a decrease in IQ and a decreased ability to perform in cognitive tasks, however these changes caused by smoking cannabis are not irreversable[factual?].
Cannabis use disorder is caused by a prolonged and chronic use of the drug and is defined in the fifth revision of the DSM5 and requires treatment.
Suicidal tendencies/ideations Regular and prolonged cannabis use has been shown to trigger suicidal ideation in users in their twenties with a high correlattion observed between regular cannabis use and suicidal attempts and ideation[7]. Also, interestingly, people who smoke cannabis before the age of 17 are 3.5 times more likely to attempt suicide as those who stated smoking later in life[8].
Marijuana dependency An estimated 9% of users develop a dependence on cannabis to function. Dependency highly correlates with chronic use[9].

More often than not, users who experience these longer-term symptoms have incentive and drive to quit. However, once the buffer in the EC system has been dampened and a substance tolerance develops it becomes difficult to easily quit the substance. A recent study has shown that teenagers who use marijuana heavily experience withdrawal symptoms when stopping use with more than 40% reporting symptoms (Budney, Roffman, Stephens, & Walker, 2007). Results also showed that participants who experienced withdrawal symptoms were more likely to meet criteria for marijuana dependence and psychiatric disorders and encounter problems with school, work, relationships, and finances (Budney, Roffman, Stephens & Walker, 2007). In severe cases psychological therapy is used and in most cases withdrawal symptoms are likely to occur:

Withdrawal symptoms

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Cravings These can last anywhere from a few months to over a year. Some ex-users report having cravings even after many years of not using the substance.
Irritability may reduce the ability to sleep well, to work, and may affect relationships with friends and family.
Anxiousness is caused by the brain compensating for the THC it received while having canabinnoids it its system. This may inhibit the ability to fee comfortable in social situations.
Depersonalisation Is usually the result of intense anxiety and may result in loss of sense of self.

[factual?]

Cannabis and mental health

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Does cannabis help to relieve symptoms or make them worse? Does it CAUSE mental health conditions or negatively exacerbate pre existing illnesses?

THC being present in the brain has been linked to an array of unsettling psychological effects including lowered mood, depression, anxiety, worry, paranoia, and negative self perception[factual?]. As individuals are exposed to these effects, the world may seem like an unusual, frightening and hostile place.

Anxiety

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Excessive cannabis use has been shown to result in a higher prevalence of anxiety with 21% of people who used the drug in the last 10 years experiencing high levels of anxiety (Reilly et al., 1998). The prevalence of anxiety disorders in cannabis users in Australia is higher (17%) in cannabis users than those who do not use cannabis [missing something?] as per data from the National Survey of Mental Health and Well Being. Just as [how?] many studies have indicated that the most common reason for cannabis use among individuals is to reduce anxiety [improve clarity] new research has emerged to suggest an opposing argument[factual?]. Research into the relationship between cannabis use and the development of anxiety disorders has found that respondents who are dependent on cannabis were over two times more likely to have a life time diagnosis of generalised anxiety disorder (GAD)[10]. Additionally, individuals who are chronic cannabis users were over two times more likely to meet anxiety disorder and panic disorder criteria or suffer from a current anxiety disorder (Hayatbakhsh, Najman, Jamrozik, Mamun, Alati, & Bor, 2007). Other research has found that cannabis can cause acute and short lasting episodes of anxiety for those who are not habitual and chronic users (Crippa, Zuardi & Martín‐Santos, et al., 2009). When taken in high doses, cannabis can cause acute episodes of fear and anxiety with about 20-30% of users showing brief but intense anxiety reactions after the ingestion of the drug (Thomas, 1996).

Depression

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Most research in this field has focused on the long term effects of cannabis use starting in adolscence and its effect on the likelihood of developing severe depressive symptoms later in life. Brook et al. (2002) and Fergusson Horwood (2001) found a positive correlation between early onset heavy cannabis use and risk of developing depressive disorders; 30% of the 20-21 year old individuals who smoked cannabis weekly met the criteria for depression (Fergusson & Horwood, 2001). Another study found that individuals who reported using cannabis and displayed at least one symptom of cannabis dependence were 4.5 times more likely to report depressive symptoms (Bovasso, 2001). Also, users who reported using cannabis regularly were 4.6 times more likely to indicate suicide ideation and tendencies compared to sample individuals who were non cannabis abusers (Bovasso, 2001).

Psychosis

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Elimination of cannabis use would reduce the incidence of psychosis related illnesess by 8% (Arseneault, Cannon, Witton & Murray, 2004). Furthermore, several studies have indicated that psychotic disorder cases may be prevented by discouraging marijuana use among vulnerable individuals (Arseneault et. al., 2004). High intake of cannabis over an extended period of time has been known to produce hallucinations, delusions, disorientation, depersonalisation and other psychotic symptoms (Thomas, 1996). Cannabis use has been linked to earlier onset of psychotic symptoms in individuals with a vulnerability to display schizophrenic tendencies. Newly admitted chronic schizophrenia patients who had used cannabis experienced their first psychotic episode 6.9 years earlier than those who did not use the substance (Veen, Selten, Van Der Tweel, Feller, Hoek & Kahn, 2004).

Paranoia

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Paranoia is one of the most controversial emotional states as it has not been completely defined as a negative emotion. However, paranoia is associated with states of fear, anxiousness and with conspiracy beliefs or the belief that someone has a vendetta to harm the individual. A recent experimental study examined the effect of THC on the level of paranoia experienced by 121 participants who had smoked cannabis in the previous month. Participants were either given a dose of THC or a placebo. Half of the participants who were given THC reported a varying degree of paranoia while only 30% of the participants given the placebo experienced paranoia (Freeman & Freeman, 2014). THC also had negative effects on participants' mood, sense of self and induced 'anomalous sensory experiences' (Freeman & Freeman, 2014).

Psychological theory and research

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Recent research and psychological theory may be able to increase our understanding on the effect of cannabis on negative emotions and what models can be formulated to aid in treatment for cannabis dependency and cannabis use disorder. The following two approaches may shed some light on the psychological mechanisms that facilitate individuals to start using cannabis, the reason for prolonged use and the negative effects.

Problem behaviour theory

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First proposed in 1977, the problem-behaviour model was formulated in longitudinal studies using adolescents and college students and their involvement in behavior deemed undesirable by social norms and elicit forms of social sanctions (Donovan, 1996). Behaviours such as cannabis use, drinking, sexual intercourse, promiscuity and other delinquent behaviour are considered negative behaviours for adolescents. However, engaging in these behaviours can be part of a psychosocial development transition and evolution into maturity (Donovan & Jessor, 1985). These behaviours were formed into a "syndrome" and emerged from analysis of two longitudinal studies carried out on college and high school students (Donovan & Jessor, 1985). The studies concluded that behaviours such as cannabis use positively correlated with environment and personality variables (Donovan & Jessor, 1985). Within the problem-behaviour framework are three distinct variables which may give an indication of the likelihood and severity of problem behaviour (Donovan & Jessor, 1985). The three systems work as a way of identifying factors which could explain problem behaviour:

  1. The personality system encompasses beliefs, attitudes values and expectations which underlie the overall willingness to engage in delinquent behaviour (Petraitis, Flay & Miller, 1995).
  2. The environment system includes the perceived influence from social circles and families to engage in behaviour (Donovan & Chase, 1980).
  3. The behaviour system refers to the amount of participation in problem behaviours.

The research using this model has been shown to account for approximately 50% of variance in marijuana use with both cross-sectional and longitudinal studies being conducted to prove it's validity even today (Donovan, 1996). The results have showed that the problem behaviour theory maintains its enduring validity in regards to cannabis use (Donovan, 1996).

The emotional stress model

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Increased cannabis use may be a result of stressful life circumstances{{fact]}. Evidence suggests that cannabis use to alleviate anxiety, depressed moods and other negative emotional states caused by stressful life events may result in an increased severity of addiction, greater distress and a decline in mental health (Brodbeck, Matter, Page, & Moggi, 2007). The emotional stress model provides a framework to examine stress as a factor and predictor for drug abuse. The model explains that individuals who use illicit substances are usually emotionally distressed or have a predisposition to negative emotional states. The model also describes that the likelihood of individuals engaging in the use of illicit substances to ease and hopefully eliminate distress and other negative emotional states (Russel & Mehrabian, 1974). Stressors that could predict the likelihood of substance abuse include events such as family dysfunction, traumatic stress and negative life events. One study estimated that 97% of cannabis-using participants aged 16 to 22 years used cannabis as a way to relax and 58% used cannabis to cope with stressful life events (Boys, Marsden, & Strang, 2001).

Intervention and therapy

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Much of the research and theoretical framework has been used to build models to aid the treatment of cannabis dependency and resolve negative emotional consequences. Demand for psychological treatment and intervention for chronic and problematic cannabis use has increased during the early part of the 21st century (Budney, Moore, Rocha & Higgins, 2006; Nordstrom & Levin, 2007). In response, psychologists recommend a combination of these three approaches which have been shown to be most effective with a 27% abstinence rate over a 14 month time period (Zvolensky, Vujanovic, Bernstein, Bonn-Miller, Marshall, & Leyro, 2007).

Motivational Enhancement Therapy The first stage in therapy uses motivational interviewing to help identify how the substance has affected lifestyle, emotional, and psychological well-being. The initiative is to help clients see how their drug abuse affects their short- and long-term goals. This will hopefully help the client realise that cannabis dependency is negatively impacting their life and motivate them to quit.[11]
Cognitive Behavioral Therapy CBT offers the client the opportunity to role play with the therapist in various scenarios to help prepare the client if they find themselves in situations where cannabis use is likely. Therapy also includes relaxation techniques and alternative ways to alleviate depressed moods.[12]
Contingency Management was initially derived from techniques developed for cocaine and other drug abusers and uses a schedule in which the client would earn a predetermined amount of cash vouchers for time period milestones reached substance free. The final part of the intervention program monitors clients by periodic urine testing.[13]

Quiz time!

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Here is a short quiz to test your knowledge on the negative effect cannabis has on emotion:

1 In the case study, Jim displays the following symptoms:

Cannabis dependency
Cannabis use disorder
Anxiety
Depression
All of the above

2 THC affects the endocannibinoid system (EC) system by:

Causing brain damage
Impairing the ability of natural neurons to communicate effectively
Restricting blood flow
Causing an epileptic fit
Multiplying neurotransmitters

3 What is the MOST common short-term negative emotional side effect of cannabis use?

Paranoia
Psychosis
Depressed mood
Anxiety
Cannabis dependency

4 What therapy is used in conjunction with cognitive behavioural therapy and motivational enhancement therapy to treat the negative effects of cannabis abuse?

ECT
Contingency management
Therapeutic medication
Hypnosis
All of the above


Conclusion

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The effect of cannabis on emotional states is a hot topic of debate and an interesting field of research. The effect that cannabis has on our brain chemistry is profound yet still unclear. More research may be needed to fully understand the effect of THC on the endocannibinoid system. There is, however, evidence to suggest that cannabis does exacerbate existing conditions and may induce negative emotional states for a short period of time. Long-term, cannabis has been associated with the development of depressive, anxiety, and panic disorders. The main theory to explain the effects of excessive cannabis uses life stressors to understand the cause of cannabis use. Using Problem Behavior Theory and the Emotional Distress Model, treatment utilising cognitive behavioural therapy (CBT), motivational enhancement theory (MET) and finally contingency management has been found to be the most effective.

See also

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References

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Barceloux, Donald G (20 March 2012). "Chapter 60: Marijuana (Cannabis sativa L.) and synthetic cannabinoids". Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. John Wiley & Sons. p. 915.

Boys, A., Marsden, J., & Strang, J. (2001). Understanding reasons for drug use amongst young people: a functional perspective. Health education research,

16(4), 457-469. doi: 10.1093/her/16.4.457

Brodbeck, J., Matter, M., Page, J., & Moggi, F. (2007). Motives for cannabis use as a moderator variable of distress among young adults. Addictive Behaviors, 32, 1537−1545. doi: 10.1016/j.addbeh.2006.11.012

Brook, D., Brook, J., Zhang, C., Cohen, P. & Whiteman, M. (2002) Drug use and the risk of major depressive disorder, alcohol dependence, and substance use disorders. Archives of General Psychiatry, 59, 1039–1044. doi: 10.1001/archpsyc.59.11.1039

Budney, A. J., Roffman, R., Stephens, R. S., & Walker, D. (2007). Marijuana Dependence and Its Treatment. Addiction Science & Clinical Practice4(1), 4–16.

Carroll, K. M., Easton, C. J., Nich, C., Hunkele, K. A., Neavins, T. M., Sinha, R., ... & Rounsaville, B. J. (2006). The use of contingency management and motivational/skills-building therapy to treat young adults with marijuana dependence. Journal of consulting and clinical psychology,74(5), 955.

Crippa, J. A., Zuardi, A. W., Martín‐Santos, R., Bhattacharyya, S., Atakan, Z., McGuire, P., & Fusar‐Poli, P. (2009). Cannabis and anxiety: a critical review of the evidence. Human Psychopharmacology: Clinical and Experimental24(7), 515-523.

Donovan, J. E. (1996). Problem-behavior theory and the explanation of adolescent marijuana use. Journal of drug issues26(2), 379-404.

Fergusson, D. M. & Horwood, L. J. (2001) The Christchurch Health and Development Study: review of findings on child and adolescent mental health. Australian and New Zealand Journal of Psychiatry, 35, 287–296. doi: 10.1046/j.1440-1614.2001.00902.x

Freeman, D., & Freeman, J. (2014). Cannabis really can trigger paranoia. Psychology, p. 1. Retrieved October 22, 2016, fromhttp://www.theguardian.com/science/2014/jul/16/cannabis-paranoia-psychoactive-thc-mood

Green, B., Kavanagh, D., & Young, R. (2003). Being stoned: a review of self‐reported cannabis effects. Drug and Alcohol Review, 22(4), 453-460. doi: 10.1080/09595230310001613976

Hall, W., & Solowij, N. (1998). Adverse effects of cannabis. The Lancet,352(9140), 1611-1616. doi: 10.1016/S0140-6736(98)05021-1 Hathaway, A. D. (2003). Cannabis effects and dependency concerns in long-term frequent users: a missing piece of the public health puzzle. Addiction Research & Theory, 11(6), 441-458. doi: 10.1080/1606635021000041807

Hayatbakhsh, M. R., Najman, J. M., Jamrozik, K., Mamun, A. A., Alati, R., & Bor, W. (2007). Cannabis and anxiety and depression in young adults: a large prospective study. Journal of the American Academy of Child & Adolescent Psychiatry46(3), 408-417.

Jessor, R., Chase, J. A., & Donovan, J. E. (1980). Psychosocial correlates of marijuana use and problem drinking in a national sample of adolescents.American Journal of Public Health, 70(6), 604-613. doi: 10.2105/AJPH.70.6.604

Johnson, BA (1990). "Psychopharmacological effects of cannabis". British journal of hospital medicine43 (2): 114–6, 118–20, 122

Madras, B. K. (2014). "Dopamine challenge reveals neuroadaptive changes in marijuana abusers". Proceedings of the National Academy of Sciences111 (33): 11915–11916. doi:10.1073/pnas.1412314111. ISSN 0027-8424. PMC 4143049. PMID 25114244.

McLaren, J., Mattick, R.P. (2010). Cannabis in Australia: Use, supply, harms, and responses. Retrieved from Australian Government Department of Health and Aging website: http://www.health.gov.au/internet/drugstrategy/publishing.nsf/Content/4FDE76ABD582C84ECA257314000BB6EB/$File/mono-57.pdf

Mehrabian A., Russell, J. A. (1974). An approach to environmental psychology (1 ed.). Cambridge, Mass.: MIT Press

Nordstrom, B. R., & Levin, F. R. (2007). Treatment of cannabis use disorders: a review of the literature. The American Journal on Addictions, 16(5), 331-342. doi: 10.1080/10550490701525665

Pedersen W. Does cannabis use lead to depression and suicidal behaviours? A population-based longitudinal study. Acta Psychiatr Scand. 2008 Nov;118(5):395-403. doi: 10.1111/j.1600-0447.2008.01259.x. Epub 2008 Sep 16. PubMed PMID: 18798834.

Petraitis, J., Flay, B. R., & Miller, T. Q. (1995). Reviewing theories of adolescent substance use: organizing pieces in the puzzle. Psychological bulletin, 117(1), 67.

Ramikie, T., S., Nyilas, R., Bluett, R., Gamble-George, J., C., Hartley, N. D., Mackie, K., Masahiko, W., Katona, I., Patel, S. (2014) Multiple Mechanistically Distinct Modes of Endocannabinoid Mobilization at Central Amygdala Glutamatergic Synapses, Neuron, vol 18 (5), 1111-1125 doi http://dx.doi.org/10.1016/j.neuron.2014.01.012

Rielly, D., Didcott, P., Swift, W, Hall, W., (1998). Long-term cannabis use: characteristics of users in an Australian rural area. Addiction, 93(6), 837-846. DOI: 10.1046/j.1360-0443.1998.9368375.x

Thomas, H. (1996). A community survey of adverse effects of cannabis use.Drug and alcohol dependence, 42(3), 201-207. doi:10.1016/S0376-8716(96)01277-X

Van Ours, J. C., Williams, J., Fergusson, D., & Horwood, L. J. (2013). Cannabis use and suicidal ideation. Journal of Health Economics32(3), 524-537.

Walker, Denise D., et al. "Motivational enhancement therapy for adolescent marijuana users: A preliminary randomized controlled trial." Journal of Consulting and Clinical Psychology 74.3 (2006): 628.

Zvolensky, M. J., Vujanovic, A. A., Bernstein, A., Bonn-Miller, M. O., Marshall, E. C., & Leyro, T. M. (2007). Marijuana use motives: A confirmatory test and evaluation among young adult marijuana users.Addictive behaviors32(12), 3122-3130.

  1. Ramikie, T., S., Nyilas, R., Bluett, R., Gamble-George, J., C., Hartley, N. D., Mackie, K., Masahiko, W., Katona, I., Patel, S. (2014) Multiple Mechanistically Distinct Modes of Endocannabinoid Mobilization at Central Amygdala Glutamatergic Synapses, Neuron, vol 18 (5), 1111-1125 doi http://dx.doi.org/10.1016/j.neuron.2014.01.012
  2. Ramikie, T., S., Nyilas, R., Bluett, R., Gamble-George, J., C., Hartley, N. D., Mackie, K., Masahiko, W., Katona, I., Patel, S. (2014) Multiple Mechanistically Distinct Modes of Endocannabinoid Mobilization at Central Amygdala Glutamatergic Synapses, Neuron, vol 18 (5), 1111-1125 doi http://dx.doi.org/10.1016/j.neuron.2014.01.012
  3. Ramikie, T., S., Nyilas, R., Bluett, R., Gamble-George, J., C., Hartley, N. D., Mackie, K., Masahiko, W., Katona, I., Patel, S. (2014) Multiple Mechanistically Distinct Modes of Endocannabinoid Mobilization at Central Amygdala Glutamatergic Synapses, Neuron, vol 18 (5), 1111-1125 doi http://dx.doi.org/10.1016/j.neuron.2014.01.012
  4. Madras, B. K. (2014). "Dopamine challenge reveals neuroadaptive changes in marijuana abusers"Proceedings of the National Academy of Sciences111 (33): 11915–11916. doi:10.1073/pnas.1412314111ISSN 0027-8424PMC 4143049PMID 25114244.
  5. Barceloux, Donald G (20 March 2012). "Chapter 60: Marijuana (Cannabis sativa L.) and synthetic cannabinoids". Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. John Wiley & Sons. p. 915.
  6. Johnson, BA (1990). "Psychopharmacological effects of cannabis". British journal of hospital medicine43 (2): 114–6, 118–20, 122
  7. Pedersen W. Does cannabis use lead to depression and suicidal behaviours? A population-based longitudinal study. Acta Psychiatr Scand. 2008 Nov;118(5):395-403. doi: 10.1111/j.1600-0447.2008.01259.x. Epub 2008 Sep 16. PubMed PMID: 18798834.
  8. Van Ours, J. C., Williams, J., Fergusson, D., & Horwood, L. J. (2013). Cannabis use and suicidal ideation. Journal of Health Economics32(3), 524-537.
  9. Pedersen W. Does cannabis use lead to depression and suicidal behaviours? A population-based longitudinal study. Acta Psychiatr Scand. 2008 Nov;118(5):395-403. doi: 10.1111/j.1600-0447.2008.01259.x. Epub 2008 Sep 16. PubMed PMID: 18798834.
  10. Hayatbakhsh, M. R., Najman, J. M., Jamrozik, K., Mamun, A. A., Alati, R., & Bor, W. (2007). Cannabis and anxiety and depression in young adults: a large prospective study. Journal of the American Academy of Child & Adolescent Psychiatry46(3), 408-417.
  11. Walker, Denise D., et al. "Motivational enhancement therapy for adolescent marijuana users: A preliminary randomized controlled trial." Journal of Consulting and Clinical Psychology 74.3 (2006): 628.
  12. Nordstrom, B. R., & Levin, F. R. (2007). Treatment of cannabis use disorders: a review of the literature. The American Journal on Addictions, 16(5), 331-342. doi: 10.1080/10550490701525665
  13. Carroll, K. M., Easton, C. J., Nich, C., Hunkele, K. A., Neavins, T. M., Sinha, R., ... & Rounsaville, B. J. (2006). The use of contingency management and motivational/skills-building therapy to treat young adults with marijuana dependence. Journal of consulting and clinical psychology,74(5), 955.