Dr. Upali P. K. Peris, Dr. Monday N. Igwe, Dr. Ruwan M Jayatunge
Abstract
Cannabis sativa (marijuana) which has been used throughout the world for thousands of years has been established to exert significant negative effects on the physical and mental health as well as social and occupational functioning of users. Cannabis abuse can also have profound negative effects on families and communities. Despite these, the prevalence of marijuana abuse and dependence disorders has been increasing recently among adults and adolescents. Prevention and intervention programs for marijuana abuse are highly essential. Early intervention initiatives and psycho education strategies are important in preventive actions.
Introduction
Cannabis sativa (marijuana) has been used throughout the world medically, recreationally and spiritually for thousands of years (Maule, 2015). It is the most commonly used illicit drug in the world (Wittchen et al., 2009). Despite being illegal in many countries, it is easily obtained and even homegrown (Delisi et al., 2006). According to the results from the 2011 National Survey on Drug Use and Health, the rate of marijuana use has had a steady increase since 2007. Cannabis use continues to constitute a social and public health problem.
The cannabis plant (Cannabis sativa) has a long history of use both as a medicinal agent and intoxicant (ElSohly & Slade, 2005). There are over 400 chemicals in marijuana. The active compounds of cannabis, called cannabidiols, have 64 active isomers. Only one metabolite, tetrahydrocannabinol (THC) is reported to be an active metabolite responsive to its effects (Morrison et al., 2009). THC usually refers to the naturally occurring isomer of delta-9-THC, but it may also include delta-8-THC. The delta-9-tetrahydrocannabinol contains psychoactive properties. Marijuana produces a number of characteristic behaviors in humans and animals, including memory impairment, antinociception, and locomotor and psychoactive effects (Sim-Selley, 2003).
THC leads to increased activation in frontal and paralimbic regions and the cerebellum (Chang & Chronicle, 2007).Cannabinoids act on a specific receptor that is widely distributed in the brain regions involved in cognition, memory, reward, pain perception, and motor coordination (Adams & Martin, 1996). Cannabis produces euphoria and relaxation, perceptual alterations, time distortion, and the intensification of ordinary sensory experiences (Hall, Solowij & Lemon 1994).
Although most people who smoke cannabis will develop neither severe mental health problems nor dependence, regular use of cannabis may be associated with a range of health, emotional, behavioural, social, and legal problems, particularly in young, pregnant, and severely mentally ill people (Winstock, Ford & Witton, 2010). Cannabis users who also smoke tobacco are more dependent on cannabis, have more psychosocial problems and have poorer cessation outcomes than those who use cannabis but not tobacco (Peters, Budne & Carroll 2012).
Epidemiological studies indicate that approximately 10% of lifetime cannabis users meet the criteria for cannabis abuse or dependence (Anthony et al., 1994; Cottler et al., 1995; Hall et al., 1999). The epidemiological literature shows that cannabis use increases the risk of accidents (Hall, 2015) and risk of motor vehicle crashes (Hall & Degenhardt, 2009). Cannabis is currently one of the leading substances reported in arrests (Dennis et al., 2002).
Tolerance and dependence to cannabinoids develop after chronic use, as demonstrated both clinically and in animal models (Sim-Selley, 2003). According to Levin and colleagues (2011) Cannabis dependence is a substantial public health problem. A large body of evidence now demonstrates that cannabis dependence, both behavioral and physical, does occur in about 7-10% of regular users, and that early onset of use, and especially of weekly or daily use, is a strong predictor of future dependence (Kalant, 2004). Cannabis dependence or cannabis use disorder is defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a condition requiring treatment (Gordon Conley & Gordon, 2013).
Cannabis withdrawal is an important component of cannabis dependence (Lee et al., 2014). As many as 85% of users experience withdrawal (Budney et al., 2004; Winstock et al., 2010). Cannabis withdrawal is characterized by craving, irritability, nervousness, depressed mood, restlessness, sleep difficulty, and anger. With the recent publication of the DSM-5, a cannabis withdrawal syndrome is now officially recognized with defined criteria (APA, 2013).
Consequences of Cannabis Use
Studies show significant negative effects of smoking marijuana on physical and mental health as well as social and occupational functioning (Gazdek, 2014). Smoking marijuana is known to have hemodynamic consequences (Mittleman et al., 2001). Cannabis also has immunosuppressant and endocrine effects although the clinical significance of these is still not clear (Ashton, 2001). Cannabis smoking shows a dose-response relation with pulmonary risk in the same way that tobacco smoking does. Although problems of cannabis use can arise at any level of use, however low, cannabis use disorders and other problems are more likely to arise in long term, heavy daily users than in casual, infrequent users. (Winstock, et al., 2010).
Longitudinal association between cannabis use and mental health has been studied by the researchers. Cannabis use is a known risk factor for a range of mental health problems (van Gastel et al., 2014). Cannabis use has been associated with several adverse life outcomes, including unemployment, legal problems, dependence and early school leaving (Serafini et al., 2013). Furthermore, Monshouwer and colleagues (2006) specify that cannabis use is associated with aggression and delinquency. In addition, Fergusson and Boden (2008) point out that greater welfare dependence and lower relationship and life satisfaction associated with cannabis abuse.
Majority of studies have suggested a significant cognitive decline in cannabis abusers compared to non-abusers and healthy controls (Shrivastava et al., 2011; Solowij, 1988). According to Kalant (2004) Cannabis use has been linked to a number of both short- and long-term health consequences, including depression, paranoia, learning problems, memory deficits, and attention deficits. In addition, Cannabis use also causes symptoms of depersonalization, fear of dying and irrational panic ideas (Khan & Akella 2009). Also, cannabis use significantly increases the risk of manic symptoms (Henquet, Krabbendam & Graaf, 2006) and mania (Leweke & Koethe, 2008). Evidence indicates that cannabis use is considerably associated with both attempted and completed suicides among healthy youths (Serafini et al., 2013; Price et al., 2009).
Cannabis intoxication can occur shortly after cannabis use. The intoxication by cannabis is associated with subjective symptoms of euphoria, perceptual distortion, continuous giggling, sedation, lethargy, impaired perception of time, difficulties in the performance of complex mental processes, impaired judgment and social withdrawal (Crippa et al. 2012). Some clinicians have noticed panic attacks with cannabis intoxication. Cannabis intoxication symptoms are usually gone after a maximum of one week abstinence (Lishman, 1988).
Heavy cannabis use could lead to an ‘amotivational syndrome which has been described as personality deterioration with loss of energy and drive to work (Tennant & Groesbeck, 1972; Johns, 2001). Cannabis-induced amotivational syndrome negatively impacts volition, self-care and social performance.
Cannabis-induced psychotic disorder (CIPD) refers to psychotic symptoms that arise in the context of cannabis intoxication (Morales-Muñoz et al., 2014). Cannabis use is a risk factor for the development of incident psychotic symptoms (Arendt et al, 2005; Kuepper et al., 2011) and exacerbates psychosis (Hall et al., 2004). Hall and team (2004) state that cannabis use can precipitate schizophrenia in vulnerable individuals. Deficits in prepulse inhibition (PPI) and cannabis abuse are consistently found in schizophrenia (Morales-Muñoz et al., 2015).
Cannabis use in adolescence leads to a two- to three-fold increase in the relative risk for schizophrenia or schizophreniform disorder in adulthood (Arseneault et al., 2004). The abuse of cannabis by patients with psychiatric disorders such as schizophrenia and mood and anxious disorders has a negative impact both in the acute and advanced stages of these conditions (Diehl, Cordeiro &, Laranjeira, 2010).
Exposure to marijuana during a critical period of neural development may interrupt maturation processes (Jacobus et al., 2009). Adolescents appear more adversely affected by heavy use than adults (Schweinsburg, Brown & Tapert , 2008).
Chronic cannabis use may alter brain structure and function in the adult and adolescent population (Batalla et al., 2013). Sami and colleagues (2015) suspect cannabis use may be associated with dopamine signaling alterations. Fontes and team (2011) point out that cannabis use has been associated with prefrontal cortex (PFC) dysfunction.
Arseneault and colleagues (2004) were of the view that cases of psychotic disorder could be prevented by discouraging cannabis use among vulnerable youths. Consequently Moore and team (2007) emphasize that there is sufficient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life.
According to El Marroun and team (2009) maternal cannabis use, even for a short period, may be associated with several adverse fetal growth trajectories. Cannabinoids have the ability to cross the placental barrier to the foetus and are detectable in the breast milk of mothers who use cannabis (Liebke, 2001). Current evidence indicates that cannabis use both during pregnancy and lactation, may adversely affect neurodevelopment, especially during periods of critical brain growth both in the developing fetal brain and during adolescent maturation, with impacts on neuropsychiatric, behavioural and executive functioning. (Jaques et al., 2014). Prenatal marijuana exposure is associated with adverse perinatal effects (Astley & Little, 1990).
Medical Uses of Cannabis
The use of cannabis for medical purposes is a controversial but an important topic of public and scientific interest (Ware, Adams &Guy, 2005). According to Grotenhermen and Müller-Vahl (2012) cannabinoids are useful for the treatment of various medical conditions. Medicinal marijuana has been prescribed in chronic pain management, antiepileptic treatment in partial epilepsy, symptomatic relief in multiple sclerosis and chronic neuropathic pain. However severe risks are associated with the non-medicinal use of cannabis. Hill (2015) emphasizes that physicians should educate patients about medical uses of marijuana to ensure that it is used appropriately and that patients will benefit from its use.
Although cannabis has valid medical applications, it has addictive potential. Heavy cannabis use may contribute to the development of significant psychosocial and health-related problems (Budney,, Vandrey and Stanger 2010 ). Cannabis use clearly has serious implications for young people who are particularly sensitive to its psychotogenic effects (Kolliakou et al., 2012). Early interventions are essential in treating cannabis related disorders.
Management of Cannabis Use
The prevalence of marijuana abuse and dependence disorders has been increasing among adults and adolescents. They continue to smoke the drug despite social, psychological, and physical impairments, commonly citing consequences such as relationship and family problems, guilt associated with use of the drug, financial difficulties, low energy and self-esteem, dissatisfaction with productivity levels, sleep and memory problems, and low life satisfaction ( Gruber et al , 2003 ; Budney et al, 2007).
Despite the fact that there are large numbers of people with cannabis dependence, relatively little attention has been paid to the treatment of this condition (Nordstrom & Levin, 2007) and also the preventative strategies are still limited (Deoganet al., 2015).
Pharmacological and psychological interventions are recommended for the cannabis use disorder. Allsop and team (2014)propose cannabis extract nabiximols (Sativex) as a medication for cannabis withdrawal. Levin and colleagues (2011) suggest Dronabinol for the treatment of cannabis dependence. Haney et al (2013) recommend the FDA-approved synthetic analogue of THC nabilonewhich has higher bioavailability and clearer dose-linearity than dronabinol.
Steinberg and team (2002) suggest psychosocial treatment for cannabis dependence. Among the psychological interventions Cognitive and behavioral therapies and motivational enhancement therapies have proven to be effective in cannabis withdrawal and dependence (Benyamina et al., 2008).
Motivational enhancement therapy is designed to help resolve ambivalence about quitting and strengthen motivation to change (Elkashef et al., 2008). Cognitive behavioral therapy (CBT) has demonstrated efficacy as both a monotherapy and as part of combination treatment strategies (McHugh, Hearon & Otto, 2010).
CBT for marijuana dependence has typically been delivered in 45 to 60- minute individual or group counseling sessions. The overall focus is the teaching of coping skills relevant to quitting marijuana and coping with other related problems that might interfere with good outcome. Such coping skills include functional analysis of marijuana use and cravings, development of self-management plans to avoid or cope with drug-use triggers, drug refusal skills, problem-solving skills, and lifestyle management (Elkashef et al., 2008). In addition, Litt and team (2008) highlight the efficacy of contingency management treatments for marijuana dependence.
Treatment of cannabis use among people with psychotic or depressive disorders is imperative. Available studies indicate that effectively treating the mental health disorder with standard pharmacotherapy may be associated with a reduction in cannabis use and that longer or more intensive psychological intervention rather than brief interventions may be required, particularly among heavier users of cannabis and those with more chronic mental disorders (Baker, Hides & Lubman 2010).
As a safer alternative, some propose cannabis substitution which is a method of harm reduction. Harm reduction refers to policies and programmes that aim to reduce the harms associated with the use of drugs. Cannabis substitution can be an effective harm reduction method for those who are unable or unwilling to stop using drugs completely (Lau et al., 2015). Based on principles of public health, harm reduction offers a pragmatic yet compassionate set of strategies designed to reduce the harmful consequences of addictive behavior for both drug consumers and the communities in which they live (Marlatt, 1996).
Conclusion
Cannabis abuse can have a profound effect on the health of individuals, their families, and their communities. Prevention and intervention programs for marijuana abuse are highly essential. Early intervention initiatives and psycho education strategies are important in preventive action.
Acknowledgements:
1) Mark D. Litt, Ph.D. Professor of Psychology University of Connecticut
2) Dr. Ilan Nachim, HBSc, MSc, MD, CCFP
About the Authors:
1) Dr. Upali P. K. Peris- Senior Lecturer in Psychiatry Faculty of Medicine University of Kelaniya Sri Lanka
2) Dr. Monday N. Igwe- Lecturer, Department of Psychological Medicine Ebonyi State University Abakaliki, Nigeria
3) Dr. Ruwan M. Jayatunge- Former Focal Point of Mental Health in Puttlam District. Ministry of Health in Sri Lanka
References
Adams, I.B., Martin, B.R.(1996). Cannabis: pharmacology and toxicology in animals and humans. Addiction; 91: 1585–614.
Allsop, D.J., Copeland, J. , Lintzeris, N. , Dunlop, A.J., Montebello, M. , Sadler, C. , Rivas, G.R ., Holland, R.M., Muhleisen, P. , Norberg, M.M. , Booth, J. , McGregor, I.S. (2014).Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial. JAMA Psychiatry. 71(3):281-91.
APA (2013). Diagnostic and Statistical Manual. 5th edition. Arlington: American Psychiatric Association.
Arendt, M. , Rosenberg, R., Foldager, L., Perto, G., Munk-Jørgensen, P.(2005).Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases. Br J Psychiatry. ;187:510-5.
Arseneault, L., Cannon, M., Witton, J., & Murray, R.M. (2004) Causal Associations between cannabis and psychosis: examination of the evidence. Br J Psychiatry, 184, 110- 117.
Ashton, C.(2001). Pharmacology and effects of cannabis: A brief review. Br J Psychiatry. ;178:101–6.
Astley, S.J., Little, R.E.(1990).Maternal marijuana use during lactation and infant development at one year. Neurotoxicol Teratol. ;12(2):161-8.
Baker, A.L. , Hides, L., Lubman, D.I.(2010).Treatment of cannabis use among people with psychotic or depressive disorders: a systematic review.J Clin Psychiatry. 2010 Mar;71(3):247-54.
Batalla, A., Bhattacharyya, S., Yücel, M., Fusar-Poli ,P., Crippa, J.A., Nogué, S., Torrens, M., Pujol, J., Farré, M., Martin-Santos, R. (2013).Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings.PLoS One. ;8(2):e55821.
Benyamina, A. , Lecacheux, M., Blecha, L., Reynaud, M., Lukasiewcz, M. (2008).Pharmacotherapy and psychotherapy in cannabis withdrawal and dependence.Expert Rev Neurother. ;8(3):479-91.
Budney, A.J., Hughes, J.R., Moore, B.A., Vandrey, R.(2004). Review of the validity and significance of cannabis withdrawal syndrome. Am J Psychiatry;161:1967-77
Budney, A.J. , Roffman, R., Stephens, R.S., Walker, D. (2007).Marijuana dependence and its treatment. Addict Sci Clin Pract. ;4(1):4-16.
Budney, A.J., Vandrey, R.G., Stanger, C.(2010).[Pharmacological and psychosocial interventions for cannabis use disorders].Rev Bras Psiquiatr. ;32 Suppl 1:S46-55.
Chang, L ., Chronicle, E.P.(2007).Functional imaging studies in cannabis users.Neuroscientist.;13(5):422-32.
Crippa, J.A., Derenusson, G.N., Chagas, M.H, et al.(2012).Pharmacological interventions in the treatment of the acute effects of cannabis: a systematic review of literature. Harm Reduct J. 9: 7.
Delisi, L.E, Bertisch, H.C., Szulc, K.U., Majche,r M., Brown, K., Bappal, A., Ardekani, B.A. (2006).A preliminary DTI study showing no brain structural change associated with adolescent cannabis use.Harm Reduct J. 9;3:17.
Dennis, M., Babor, T.F., Roebuck, M.C., Donaldson, J.(2002). Changing the focus: the case for recognizing and treating cannabis use disorders.Addiction. ;97 Suppl 1:4-15.
Deogan, C. , Zarabi, N., Stenström, N., Högberg, P., Skärstrand, E., Manrique-Garcia, E, Neovius, K., Månsdotter, A. (2015).Cost-Effectiveness of School-Based Prevention of Cannabis Use. Appl Health Econ Health Policy.
Diehl, A., Cordeiro, D.C., Laranjeira, R.(2010).[Cannabis abuse in patients with psychiatric disorders: an update to old evidence].Rev Bras Psiquiatr. ;32 Suppl 1:S41-5.
Elkashef ,A., Vocci, F., Huestis, M., Haney, M., Budney, A., Grube,r A., el-Guebaly, N.(2008). Marijuana neurobiology and treatment. Subst Abus.;29(3):17-29.
El Marroun, H. , Tiemeier. H., Steegers, E.A., Jaddoe, V.W., Hofman, A., Verhulst, F.C., van den Brink, W., Huizink, A.C. (2009).Intrauterine cannabis exposure affects fetal growth trajectories: the Generation R Study.J Am Acad Child Adolesc Psychiatry. ;48(12):1173-81.
ElSohly, M.A., Slade, D. (2005) Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 78:539–548.
Fergusson, D.M ., Boden, J.M.(2008).Cannabis use and later life outcomes. Addiction. 103(6):969-76; discussion 977-8
Fontes, M.A., Bolla, K.I., Cunha, P.J., Almeida, .PP., Jungerman, F., Laranjeira, R.R., Bressan, R.A., Lacerda, A.L. (2011). Frontal Assessment Battery (FAB) is a simple tool for detecting executive deficits in chronic cannabis users.J Clin Exp Neuropsychol. ;33(5):523-31.
Gazdek, D.(2014).[Marijuana for medical purposes–public health perspective]. Lijec Vjesn. 2014 Jul-Aug;136(7-8):192-9.
Gordon, A.J., Conley, J.W., Gordon, J.M.(2013).Medical consequences of marijuana use: a review of current literature. Curr Psychiatry Rep. ;15(12):419.
Grotenhermen, F. , Müller-Vahl, K.(2012). The therapeutic potential of cannabis and cannabinoids. Dtsch Arztebl Int. ;109(29-30):495-501.
Gruber, A.J. , Pope, H.G., Hudson ,J.I., Yurgelun-Todd, D.(2003).Attributes of long-term heavy cannabis users: a case-control study. Psychol Med. ;33(8):1415-22.
Hall, W., Solowij, N., Lemon, J.(1994). The health and psychological consequences of cannabis use. National Drug Strategy Monograph Series no 25. Canberra: Australian Government Publishing Service.
Hall, W., Degenhardt, L., Teesson, M.(2004).Cannabis use and psychotic disorders: an update.Drug Alcohol Rev. ;23(4):433-43.
Hall, W. , Degenhardt, L. (2009).Adverse health effects of non-medical cannabis use. Lancet. 17;374(9698):1383-91.
Hall, W. (2015).What has research over the past two decades revealed about the adverse health effects of recreational cannabis use? Addiction. ;110(1):19-35.
Haney, M., Cooper, Z.D., Bedi ,G., Vosburg, S.K., Comer, S.D., Foltin, R.W. (2013).Nabilone decreases marijuana withdrawal and a laboratory measure of marijuana relapse. Neuropsychopharmacology. ;38(8):1557-65.
Henquet, C., Krabbendam, L., de Graaf, R., et al.(2006).Cannabis use and expression of mania in the general population. J Affect Disord. ;95(1-3):103–110.
Hill, K.P. (2015).Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review. JAMA. 23-30;313(24):2474-83.
Jacobus, J., Bava, S., Cohen-Zion, M., Mahmood, O., Tapert, S.F.(2009).Functional consequences of marijuana use in adolescents. Pharmacol Biochem Behav. ;92(4):559-65.
Jaques, S.C. , Kingsbury, A. , Henshcke, P. , Chomchai, C. , Clews ,S. , Falconer, J. , Abdel-Latif ,M.E. , Feller ,J.M. , Oei ,.JL . (2014).Cannabis, the pregnant woman and her child: weeding out the myths.J Perinatol. ;34(6):417-24.
Johns , A. (2001). Psychiatric effects of cannabis. The British Journal of Psychiatry.178 (2) 116-122;
Kalant, H. (2004). Adverse effects of cannabis on health: an update of the literature since 1996. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 28(5), 849-863.
Khan, M.A., Akella ,S.(2009).Cannabis-induced bipolar disorder with psychotic features: a case report. Psychiatry (Edgmont). ;6(12):44-8.
Kolliakou, A., Fusar-Poli, P, Atakan, Z.(2012).Cannabis abuse and vulnerability to psychosis: targeting preventive services. Curr Pharm Des.;18(4):542-9.
Kuepper, R., van Os ,J., Lieb, R., Wittchen, H.U., Höfler, M., Henquet, C.(2011).Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. BMJ. 2 1;342:d738.
Lau, N. , Sales, P., Averill, S., Murphy, F., Sato, S.O., Murphy, S. (2015).A safer alternative: Cannabis substitution as harm reduction.Drug Alcohol Rev. 28.
Lee, D., Schroede, J.R., Karschner, E.L., Goodwin, R.S., Hirvonen, J., Gorelick, D.A., Huestis, M.A. (2014).Cannabis withdrawal in chronic, frequent cannabis smokers during sustained abstinence within a closed residential environment. Am J Addict. 23 (3):234-42.
Levin, F.R. , Mariani, J.J., Brooks, D.J., Pavlicova, M., Cheng, W., Nunes ,E.V. (2011).Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial.Drug Alcohol Depend. 1;116(1-3):142-50.
Leweke, F., Koethe, D. (2008).Cannabis and psychiatric disorders: it is not only addiction. Addict Biol.;13(2):264–275. Review.
Liebke, S. (2001).A Cannabis User’s Harm Reduction Handbook. Retrieved from http://citeseerx.ist.psu.edu/viewdoc/download?rep=rep1&type=pdf&doi=10.1.1.202.4159
Lishman, W.A. (1988)Organic Psychiatry: The Psychological Consequences of Cerebral Disorder. 3. Oxford: Blackwell; 1998.
Litt, M.D ., Kadden, R.M., Kabela-Cormier, E., Petry, N.M.(2008). Coping skills training and contingency management treatments for marijuana dependence: exploring mechanisms of behavior change. Addiction.103(4):638-48.
Marlatt, G.A. (1996).Harm reduction: come as you are. Addict Behav. ;21(6):779-88.
Maule, W.J.(2015).Medical uses of marijuana (Cannabis sativa): fact or fallacy? Br J Biomed Sci. ;72(2):85-91.
McHugh ,R.K ., Hearon, B.A., Otto, M.W. (2010).Cognitive behavioral therapy for substance use disorders. Psychiatr Clin North Am. 2010 Sep;33(3):511-25.
Mittleman, M.A ., Lewis, R.A., Maclure, M., Sherwood, J.B., Muller ,J.E. (2001).Triggering myocardial infarction by marijuana. Circulation. 12;103(23):2805-9.
Monshouwer, K. , VAN Dorsselaer, S., Verdurmen, J., Bogt, T.T., D.E., Graaf, R., Vollebergh, W. (2006). Cannabis use and mental health in secondary school children. Findings from a Dutch survey.Br J Psychiatry. ;188:148-53.
Moore, T.H. , Zammit, S., Lingford-Hughes, A., Barnes, T.R., Jones, P.B., Burke ,M., Lewis, G. (2007). Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review.Lancet. 28;370(9584):319-28.
Morales-Muñoz, I ., Jurado-Barba, R., Ponce, G. , Martínez-Gras, I. , Jiménez-Arriero, M.Á. Moratti, S., Rubio, G.(2014). Characterizing cannabis-induced psychosis: a study with prepulse inhibition of the startle reflex.Psychiatry Res. 15;220(1-2):535-40.
Morales-Muñoz, I. , Jurado-Barba, R., Caballero, M., Rodríguez-Jiménez, R., Jiménez-Arriero, M.Á., Fernández-Guinea, S., Rubio ,G. (2015). Cannabis abuse effects on prepulse inhibition in patients with first episode psychosis in schizophrenia. J Neuropsychiatry Clin Neurosci. ;27(1):48-53.
Morrison, P.D., Zois, V., McKeown, D.A., Lee ,T.D., Holt, D.W., Powell, J.F, et al. (2009).The acute effects of synthetic intravenous Delts9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol Med. ;31:1607–16.
Nordstrom, B.R., Levin, F.R.(2007).Treatment of cannabis use disorders: a review of the literature. Am J Addict. 16(5):331-42.
Peters ,E.N., Budney, A.J., Carroll, K.M.(2012).Clinical correlates of co-occurring cannabis and tobacco use: a systematic review.Addiction. 2012 Aug;107(8):1404-17.
Price, C, Hemmingsson, T., Lewis, G., Zammit, S., Allebeck, P. (2009).Cannabis and suicide: longitudinal study. Br J Psychiatry.195:492–710.
SAMHSA (2012) Results from the 2011 National Survey on Drug Use and Health: National Findings(Subst Abuse Ment Health Serv Admin, Rockville, MD), NSDUH Series H-30, DHHS Publication No. SMA 06-4194.
Sami, M.B. , Rabiner, E.A. , Bhattacharyya, S . (2015). Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date.Eur Neuropsychopharmacol. 2015 Mar 30. pii: S0924-977X(15)00088-7.
Schweinsburg, A.D. , Brown, S.A., Tapert, S.F.(2008).The influence of marijuana use on neurocognitive functioning in adolescents. Curr Drug Abuse Rev. ;1(1):99-111.
Serafini, G., Pompili, M., Innamorati, M., Temple, E.C., Borgwardt, S., & Girardi, P. (2013). The association between cannabis use, mental illness and suicidal behaviour: What is the role of hopelessness? Frontiers in Psychiatry, 4, 125
Shrivastava ,A., Johnston, M., Tsuang, M.(2011). Cannabis use and cognitive dysfunction..Indian J Psychiatry. ;53(3):187-91.
Sim-Selley, L.J.(2003).Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids.Crit Rev Neurobiol. 15(2):91-119
Solowij, N. (1988). Cannabis and cognitive functioning. Cambridge: Cambridge University Press.
Steinberg, K.L., Roffman, R.A., Carroll, K.M., Kabela, E., Kadden, R., Miller, M., Duresky, D. (2002).Tailoring cannabis dependence treatment for a diverse population.Addiction. ;97 Suppl 1:135-42.
Tennant, F. S.,Groesbeck, C. J. (1972) Psychiatric effects of hashish. Archives of General Psychiatry, 27, 133 -136.
van Gastel, W.A. , MacCabe ,J.H., Schubart, C.D., van Otterdijk, E., Kahn, R.S., Boks, M.P.(2014).Cannabis use is a better indicator of poor mental health in women than in men: a cross-sectional study in young adults from the general population. Community Ment Health J. ;50(7):823-30.
Ware, M.A., Adams, H., Guy, G.W.(2005). The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract. ;59(3):291-5.
Winstock, A.R., Ford, C., Witton, J. (2010).Assessment and management of cannabis use disorders in primary care. BMJ.1;340:c1571.
Wittchen, H.U., Behrendt, S., Hofler, M., Perkonigg, A., Rehm, J., Lieb, R., et al. (2009).A typology of cannabis-related problems among individuals with repeated illegal drug use in the first three decades of life: evidence for heterogeneity and different treatment needs. Drug Alcohol Depend2009;102:151-7.
