|Year : 2021 | Volume
| Issue : 6 | Page : 943-976
Cannabis associated mental health effects: A review
Neeraj Kancherla1, Keerthana Mani Jeyanthi2, Ramsha Abbas3, Thanmay Sai Charaan Reddy Sathi1, Amrita Upadhyay4, Sameer Krishna Prasad Garlapati1
1 Department of Psychiatry, King George Hospital, Visakhapatnam, Andhra Pradesh, India
2 Department of Internal Medicine, Sri Venkateshwaraa Medical College Hospital and Research Centre, Puducherry, India
3 Department of internal Medicine, Shifa College of Medicine, Islamabad, Pakistan
4 Department of Internal Medicine, Nobel Medical College Teaching Hospital, Morang, Nepal
|Date of Submission||15-May-2021|
|Date of Decision||20-May-2021|
|Date of Acceptance||28-May-2021|
|Date of Web Publication||10-Nov-2021|
King George Hospital, Visakhapatnam, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
According to the latest drift in Western countries, many lawmakers are trying to formulate policy to legalize the usage of Cannabis in the case of mentally vulnerable populations such as those suffering from depression, paranoia, and excessive anxiety. This particular trend has been due to short term success in the case of mood upliftment. Cannabis derivatives produce effects on both mood and cognitive function, which can be a double-edged sword if not followed with proper dosage. Beneficial effects, however, are limited and studies documenting those and even more meagre. Detrimental effects, especially those suffering from various hallucinating and delusional states, have been reported extensively in the literature. Here in the review article, we have tried to study and summarize various effects of Cannabis as well as Cannabis -derived products in the case of people who have various mental conditions. We have also tried to consider addiction to these substances and hence develop a framework for proper utilization of Cannabis in mentally ill people. Many clinicians are also in a dilemma when prescribing a Cannabis -based product to treat psychotic and mood-based disorders. Hence, a better understanding of the process of Cannabis -based treatment for the vulnerable population is necessary.
Keywords: Addiction, anxiety disorders, Cannabis, mood disorders, schizophrenia, therapeutics
|How to cite this article:|
Kancherla N, Jeyanthi KM, Abbas R, Sathi TS, Upadhyay A, Garlapati SK. Cannabis associated mental health effects: A review. J Pharm Bioall Sci 2021;13, Suppl S2:943-76
|How to cite this URL:|
Kancherla N, Jeyanthi KM, Abbas R, Sathi TS, Upadhyay A, Garlapati SK. Cannabis associated mental health effects: A review. J Pharm Bioall Sci [serial online] 2021 [cited 2022 Jun 26];13, Suppl S2:943-76. Available from: https://www.jpbsonline.org/text.asp?2021/13/6/943/330121
| Introduction|| |
Cannabis is a wholesome term to denote various species such as Cannabis sativa, Cannabis indica and Cannabis ruderalis. These plants provide various psychoactive substances. The resin can be obtained from the Cannabis plant and can be used in a crude and purified manner. This also includes >400 compounds which comprise cannabinoids, terpenoids, and flavonoids. The main compound which is responsible for causing the psychoactive effect is D-9-Tetrahydrocannabinol (THC). Cannabis and its derived chemical products such as cannabinoids act on cannabinoid receptors whihc are neurotransmitter released from the brain. Cannabis usually differs in bioavailability as well as pharmacokinetics and pharmacodynamics during the metabolism as compared to cannabinoids. Usually, these are of three different types-phytocannabinoids, endocannabinoids, and synthetically produced cannabinoids. Various clinical manifestations are produced with the usage of Cannabis, including a feeling of being relaxed, alteration of various cognitive functions, disorientation of time and place, decrease or increase of emotional response. There can be harmful effects such as mania, delusions, worsening of depression, and panic attacks in larger doses and extremely vulnerable people. If given intravenously, then the prime active component of Cannabis, which is THC, produces symptoms resembling schizophrenia such as memory loss, hallucination, and excessive anxiety. Amygdala as well hippocampus regions of the brain are responsible for causing depressive as well as psychotic symptoms in case of people who consume Cannabis on a chronic basis. In case of Cannabis misuse or Cannabis use disorder (CUD) cases, the individuals have been reported to be already suffering from some kind of mental conditions such as depression, schizophrenia, and bipolar disorder (BD).,,,, They usually see cannabinoids as having a therapeutic benefit for them., This association has been widely studied, with mentally unstable people being often diagnosed with suffering from CUD as well. Most of the studies have indicated that Cannabis has detrimental effects on one's health rather than medicinal effects on people. However to study both sides of these effects, further research is needed in a much wider population and in cases of various mental illnesses.[11.12] In our review, we have tried to summarize the effects of Cannabis on a plethora of mental conditions, which can help a clinician to determine the usage of Cannabis.
| Anxiety|| |
Anxiety which is also acute has been one of the most common side effects of Cannabis usage. However, many users during initial usage of this product experience a reduced amount of anxiety. Hence, it is a paradoxical situation, but the variation is usually dose-dependent where deleterious effects occur due to a stronger dosage of cannabinoids. It has been reported that in rodents, anxiolytic effects were reported with a low dosage of Cannabis and higher doses induced anxiety by affecting the hypothalamic-pituitary-adrenocortical pathway. The central amygdala is triggered by D9-THC induces anxiogenic crisis of individuals.
| Depression|| |
Cannabis and cannabinoids have been reported to be directly associated with major depressive disorders (MDDs) and worsening the depression crisis., Many studies have reported the harmful effects. However, few studies dismiss this connection in lieu of not considering many other additional variables such as excessive drug usage, poor education and upbringing issues.,, Most studies had reported the association of depression as a secondary manifestation when other chronic diseases were considered. Hence, there is a need to study a direct associative original research in this context.
| Psychosis|| |
When individuals are vulnerable to developing a psychotic illness, they use Cannabis under CUD due to extreme environmental influence. One in four individuals is dealing with this substance abuse in developed countries. Mostly chronic usage symptoms resemble the signs of schizophrenia. THC has been reported to cause increased psychosis when a higher dose is given, leading them to be in an near the edge situation mentally. A study carried out among 50,000 male patients described that young people who smoked Cannabis ended up twice as common with diagnosing mental illnesses such as schizophrenia.
| Paranoia|| |
This type of mental state causes an individual to have unnecessary fears that they might be under attack. The number of symptoms varies among patients as well. Many causes have been highlighted for the development of paranoia such as suicidal tendency, youth issues, physically being unwell, and cannabinoid usage., Abnormal salience theory,, tries to explain the effects of Cannabis triggering paranoia in individuals, which in turn is caused due to the presence of THC. Along with producing paranoia, THC also induces anxiety amongst Cannabis users by affecting the cannabinoid receptors in the brain. This particular chemical generates fears by facilitating negative emotions as well as producing disorientation.,
| Hallucinations|| |
Individuals under Cannabis usage experienced visual hallucinations and altered perceptions when D-9-THC causes changes in the brain's occipital lobe, as reported in many studies compared to certain placebo groups. There was a marked reduction in smooth functioning and decreased sensory cortex activation of visual receptors resulting in hallucination. The same was also observed through the help of EEG and MRI reports.,
| Disorientation|| |
Navigational skills of an individual also come under a scanner when due to chronic usage of cannabinoids, which causes a deleterious effect on hippocampal regions of the brain and leads to shifting of this function to extrahippocampal regions. Hence, additional regions of the brain take over the function of cognitive realignment so that the neural elements in these individuals achieve some sort of spatial recognition.
| Bipolar Disorder|| |
In one study, where over 40,000 people were recruited, the ones who were using Cannabis or derived materials had a greater chance of developing BD. With increasing dosage, leading to harmful effects in case of those people often leading to suicidal tendencies. Many users also complained of altering mood states, delayed recovery to normal situation. However, few studies have highlighted that the symptoms vary based on the type of Cannabis and the gender as well.
| Delusion|| |
Dopamine transmission is affected in the case of chronic Cannabis users by acting through two pathways, either through cannabinoid receptors or through the glutaminergic system. Various genes are known to play a role in this, such as COMT, DAT-1, and AKT-1. A specific condition called delusional zoopathy has been associated with excessive cannabinoid usage.
| Suicidal Ideation|| |
A study conducted by Christchurch Health and Development revealed that suicidal behaviours and concurrent usage of Cannabis were very strongly associated in individuals as young as 15 years of age. Apart from family issues, heterogeneity of other environmental factors can lead to this kind of behavior development, irrespective of the gender of an individual. Hence, in the case of suicidal ideation endogenous model, frequent consumption of cannabinoids with increased dose leads to increased suicidal thoughts.
| Impaired Short-Term Memory, Attention Judgement|| |
Cannabis causes memory loss in individuals with acute usage, just like alcohol with its intoxicated state of mind. However, more permanent damage is caused by chronic usage. There is a marked deficit in learning and then recalling things. Nevertheless, this has not been studied widely, especially at the chronic stage.
| Sleep Problems|| |
Initial studies on Cannabis revealed that this product helps in treating long-standing insomnia in patients. In the short-term, THC definitely improves the amount of sleep-induced. However, with its addiction, it will impair the sleep pattern in the long-term future. Synthetic cannabinoids such as nabilone and dronabinol have a positive effect on sleep apnea by making changes in serotonin pathways. Daytime sleepiness can be treated acutely with the help of Cannabidiol (CBD), and anxiety due to Posttraumatic stress disorders (PTSD) can be decreased with the help of nabilone.
| Discussion|| |
Therapeutic effects of CBD have been good in case of treatment-related to schizophrenia, but further clinical trials with a large number of population groups are required to address the uncertainties of side effects such as illicit recreational usage of Cannabis. Hence, a proper dose-dependent redressal needs to be done in understanding the pathophysiology of Cannabis on schizophrenia and various other types of paranoia.
Controlled clinical trials in the case of MDD patients need to be undertaken to understand the direct association of Cannabis with this disease process. It has been studied only as a secondary manifestation when Cannabis was used to treat other chronic pain disorders. The amount of risk in the acute usage of various types of cannabinoids has not been studied as yet related to a depressive state. Cannabis has long been tried in cases of anxiety to calm the patient. However, clinicians come under the scanner and dilemma such as situations considering the possibility of addiction and other delusional effects on its constant usage. More research is required to determine the ideal dose that clinicians can safely recommend to their patients without putting their lives in jeopardy. In cases of PTSD patients, mostly military patients have been studied. Hence, the research should include more groups of vulnerable populations of both genders and have age variations with larger sample size and having multicentric trials. Frequency, type of preparation, and when to use these compounds necessitates limited dose research in collaboration with clinicians and pharma companies. Addiction in people is common due to a variety of personal as well as societal factors. The people in the early stage are vulnerable, which later on with illicit reinforcement end up in chronic usage without a physician's consultation. This again turns into a risky situation when the individual is already suffering from deteriorating mental health conditions. Hence, they try to self-medicate themselves, common in the case of patients with schizophrenia. Hence, the recreational effects outweigh the therapeutic benefits, if at all present, which needs to be checked by law enforcement officials and clinicians so that many people do not end up in a harmful situation.
| Conclusion|| |
A paradox has been created between the detrimental physical and social implications and the consumers' self-proclaimed medicinal effects for the usage of Cannabis and its derivatives. Therefore, further documented research is necessary so that the general public who wish to use Cannabis can make their own choices with an informed background.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gloss D. An overview of products and bias in research. Neurotherapeutics 2015;12:731-4.
El Sohly M, Gul W. Constituents of Cannabis sativa
. In: Pertwee R, editor. Hand Book of Cannabis
. Oxford, UK: Oxford University Press; 2014. p. 1093.
Mechoulam R, Parker LA. The endocannabinoid system and the brain. Annu Rev Psychol 2013;64:21-47.
D'Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT, et al.
The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: Implications for psychosis. Neuropsychopharmacology 2004;29:1558-72.
Yücel M, Solowij N, Respondek C, Whittle S, Fornito A, Pantelis C, et al.
Regional brain abnormalities associated with long-term heavy Cannabis
use. Arch Gen Psychiatry 2008;65:694-701.
Buckner JD, Schmidt NB, Lang AR, Small JW, Schlauch RC, Lewinsohn PM. Specificity of social anxiety disorder as a risk factor for alcohol and Cannabis
dependence. J Psychiatr Res 2008;42:230-9.
Bujarski SJ, Galang JN, Short NA, Trafton JA, Gifford EV, Kimerling R, et al. Cannabis
use disorder treatment barriers and facilitators among veterans with PTSD. Psychol Addict Behav 2016;30:73-81.
Charilaou P, Agnihotri K, Garcia P, Badheka A, Frenia D, Yegneswaran B. Trends of Cannabis
use disorder in the inpatient: 2002 to 2011. Am J Med 2017;130:678-87.e7.
Lev-Ran S, Le Foll B, McKenzie K, George TP, Rehm J. Cannabis
use and Cannabis
use disorders among individuals with mental illness. Compr Psychiatry 2013;54:589-98.
Bonn-Miller MO, Boden MT, Bucossi MM, Babson KA. Self-reported Cannabis
use characteristics, patterns and helpfulness among medical Cannabis
users. Am J Drug Alcohol Abuse 2014;40:23-30.
Sexton M, Cuttler C, Finnell JS, Mischley LK. A cross sectional survey of medical Cannabis
users: Patterns of use and perceived efficacy. Cannabis
Cannabinoid Res 2016;1:131-8.
Hasin DS, Kerridge BT, Saha TD, Huang B, Pickering R, Smith SM, et al
. Prevalence and correlates of dsm-5 Cannabis
use disorder, 2012–2013: Findings from the national epidemiologic survey on alcohol and related conditions – III. Am J Psychiatry 2016;173:588-99.
Crippa JA, Zuardi AW, Martín-Santos R, Bhattacharyya S, Atakan Z, McGuire P, et al. Cannabis
and anxiety: A critical review of the evidence. Hum Psychopharmacol 2009;24:515-23.
Bahorik AL, Leibowitz A, Sterling SA, Travis A, Weisner C, Satre DD. Patterns of marijuana use among psychiatry patients with depression and its impact on recovery. J Affect Disord 2017;213:168-71.
Moitra E, Anderson BJ, Stein MD. Reductions in Cannabis
use are associated with mood improvement in female emerging adults. Depress Anxiety 2016;33:332-8.
Danielsson AK, Lundin A, Agardh E, Allebeck P, Forsell Y. Cannabis
use, depression and anxiety: A 3-year prospective population-based study. J Affect Disord 2016;193:103-8.
Feingold D, Weiser M, Rehm J, Lev-Ran S. The association between Cannabis
use and mood disorders: A longitudinal study. J Affect Disord 2015;172:211-8.
Østergaard ML, Nordentoft M, Hjorthøj C. Associations between substance use disorders and suicide or suicide attempts in people with mental illness: A Danish nation-wide, prospective, register-based study of patients diagnosed with schizophrenia, bipolar disorder, unipolar depression or personality disorder. Addiction 2017;112:1250-9.
Andréasson S, Engström A, Allebeck P, Rydberg U. Cannabis
and schizophrenia a longitudinal study of Swedish conscripts. Lancet 1987;330:1483-6.
Ronald A, Sieradzka D, Cardno A, Haworth C, McGuire P, Freeman D. Characterization of psychotic experiences in adolescence using the Specific Psychotic Experiences Questionnaire (SPEQ): Findings from a study of 5000 16 year old twins. Schizophr Bull 2013;40:868-77.
Bebbington PE, McBride O, Steel C, Kuipers E, Radovanovic M, Brugha T, et al.
The structure of paranoia in the general population. Br J Psychiatry 2013;202:419-27.
Freeman D, McManus S, Brugha T, Meltzer H, Jenkins R, Bebbington P. Concomitants of paranoia in the general population. Psychol Med 2011;41:923-36.
Kapur S. Psychosis as a state of aberrant salience: A framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry 2003;160:13-23.
Henquet C, Di Forti M, Murray RM, van Os J. The role of Cannabis
in inducing paranoia and psychosis. In: Freeman D, Bentall R, Garety P, editors. Persecutory Delusions. Oxford: Oxford University Press; 2008. p. 267-80.
Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S, Winton-Brown T, et al.
Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 2010;35:764-74.
Ffytche DH, Howard RJ, Brammer MJ, David A, Woodruff P, Williams S. The anatomy of conscious vision: An fMRI study of visual hallucinations. Nat Neurosci 1998;1:738-42.
Hubl D, Koenig T, Strik WK, Garcia LM, Dierks T. Competition for neuronal resources: How hallucinations make themselves heard. Br J Psychiatry 2007;190:57-62.
Ford JM, Roach BJ, Jorgensen KW, Turner JA, Brown GG, Notestine R, et al.
Tuning in to the voices: A multisite FMRI study of auditory hallucinations. Schizophr Bull 2009;35:58-66.
Atakan Z. Cannabis, a complex plant: Different compounds and different effects on individuals. Ther Adv Psychopharmacol. 2012;2:241-54. doi: 10.1177/2045125312457586. PMID: 23983983; PMCID: PMC3736954.
Zorrilla I, Aguado J, Haro J, Barbeito S, Lopez Zurbano S, Ortiz A, et al
and bipolar disorder: Does quitting Cannabis
use during manic/mixed episode improve clinical/functional outcomes? Acta Psychiatr Scand 2015;131:100-10.
Mitra S, Mishra AK, Anwar Z, Lavania S. Cannabis
and delusional zoopathy: A mole that ran amok. Asian J Psychiatr 2017;30:35-6.
van Ours JC, Williams J, Fergusson D, Horwood LJ. Cannabis
use and suicidal ideation. J Health Econ 2013;32:524-37.
Dittrich A, Battig K, Zeppelin LV. Effects of (-)-delta-9-tetrahydrocannabinol (delta-9- THC) on memory, attention and subjective state. Psychopharmacologia 1973;33:369-76.
Babson KA, Sottile J, Morabito D. Cannabis
, cannabinoids, and sleep: A review of the literature. Curr Psychiatry Rep 2017;19:23.