Cannabidiol (CBD) does not make cannabis safer
Amir Englund et al reported in Neuropsychopharmacology in A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios that CBD did not protect against the adverse effect of THC. These included impaired delayed verbal recall ( p?=?0.001) and induced positive psychotic symptoms on the PANSS ( p?=?2.41?×?10–5).
Editors Note: Not only does marijuana impair memory, it is a risk factor the onset of bipolar disorder and schizophrenia. When pot is used by a person with a unipolar or bipolar mood disorder, there are increases in depression and anxiety and an overall less favorable course of illness. If a person with a mood disorder uses heavy amounts of marijuana, they could consider buying N-acetylcysteine (NAC) 500mg and increasing the dose to 1,000mg twice a day within a week as this has been shown to decrease drug use compared to placebo in adolescents and young adults using and abusing pot. Most people who sell pot, are not well-informed about its dangers and just want to make money.
Cannabis Withdrawal Syndrome Occurs in Almost Half of Regular Users
A recent systematic review and meta-analysis by researcher Anees Bahji and colleagues in the open access medical journal JAMA Network Open describes the symptoms and prevalence of cannabis withdrawal syndrome.
The most recent edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) indicates that cannabis withdrawal syndrome “requires the presence of at least 3 of the following symptoms developing within 7 days of reduced cannabis use: (1) irritability, anger, or aggression; (2) nervousness or anxiety; (3) sleep disturbance; (4) appetite or weight disturbance; (5) restlessness; (6) depressed mood; and (7) somatic symptoms, such as headaches, sweating, nausea, vomiting, or abdominal pain.”
According to Bahji and colleagues, cannabis withdrawal syndrome occurred in 47% of regular users. Higher rates of withdrawal were found among those in clinical settings, those who also used tobacco or other substances, and those who used cannabis daily.
Bahji and colleagues write that while many people believe that cannabis is relatively harmless, it actually has a variety of associated risks. Short-term risks include impaired short-term memory and motor coordination, altered judgment, paranoia, and psychosis. Long-term effects include addiction, altered brain development, poor educational outcomes, cognitive impairment, diminished quality of life, increased risk of chronic respiratory tract and psychotic disorders, injuries, motor vehicle collisions, and suicide.
The researchers warned that users of cannabis may resume cannabis use to allay the depression and anxiety symptoms that are part of the withdrawal syndrome, perpetuating the long-term withdrawal cycle.
Bahji and colleagues suggest that because of the high prevalence of the withdrawal syndrome, doctors should screen patients for cannabis withdrawal, particularly men and frequent cannabis users. They write, “Clinicians should be aware of CWS as it is associated with clinically significant symptoms, which can trigger resumption of cannabis use and serve as negative reinforcement for relapse during a quit attempt.” Doctors can offer support for those reducing their cannabis consumption.
Cannabis Use in Adolescence Linked to Depression and Suicidality in Young Adulthood
In a meta-analysis published in the journal JAMA Psychiatry in 2019, researcher Gabriella Gobbi and colleagues analyzed findings from 11 studies including a total of 23,317 participants and found that cannabis use in adolescence (before age 18) was associated with a significantly increased risk of depression, suicidality, and suicide attempts in young adulthood (between 18 and 32 years of age).
The researchers did not find a link between cannabis use and anxiety.
Editor’s Note: Cannabis use is not as harmless as many teens may believe.
Cannabis May Produce More Brain Changes in Teens with Bipolar Disorder than in Healthy Teens
At the 2019 meeting of the International Society for Bipolar Disorders, researcher Benjamin Goldstein of Sunnybrook Research Institute in Toronto reported that adolescents with bipolar disorder who smoked marijuana had greater deficits in certain brain areas than did adolescents who did not have bipolar disorder. The areas affected included the dorsal lateral and rostral middle frontal cortex, and middle cortex. Goldstein concluded, “Adolescents with [bipolar disorder] may be particularly sensitive to the neurostructural effects of cannabis.”
Marijuana in general causes adverse changes in brain structure and cognition and vulnerability to paranoia and psychosis. Heavy use in adolescence is associated with an increased incidence of the onset of bipolar disorder and schizophrenia. The Goldstein data suggest several possible causal mechanisms. Those with bipolar disorder may already have brain abnormalities that are exacerbated by marijuana use. Alternatively, marijuana and bipolar disorder together may impact brain structure more than either factor alone would.
Recent Cannabis Use Linked to Greater Symptoms of Anxiety and Mood Disorders and Less Response to Treatment
In a 2018 systematic literature review published in the Journal of Clinical Psychiatry, researcher George Mamman and colleagues reported that across 12 studies of people with anxiety and mood disorders, participants who had used cannabis in the previous six months had more symptoms than those who had used less cannabis or no cannabis during that period.
The 12 studies reviewed included a total of 11,959 participants. Four studies looked at post-traumatic stress disorder (PTSD), one at panic disorder, five at bipolar disorder, and 2 at depressive disorder. In addition to finding that recent cannabis use was associated with greater symptoms, the authors of the review also found that in 10 of the 12 studies, recent cannabis use was associated with less symptom improvement in response to treatment for bipolar disorder, depression, and PTSD; including both medication and psychotherapy.
In bipolar disorder, cannabis use was associated with greater symptom severity. Cannabis use for more than one year was linked to more recurrences of mania and shortened time to a recurrence. Compared to participants with no prior use of cannabis, those with a cannabis use disorder had more depressive symptoms, including sleep troubles and loss of interest in activities one had previously enjoyed.
In PTSD, any cannabis use at the beginning of the analysis period and sustained use of cannabis over time were both linked to greater symptom severity in the four months following the beginning of the analysis.
Mammen and colleagues cautioned that these results are limited based on the differences in measurements across the 12 studies, the inpatient populations under study, and the uncontrolled nature of the cannabis the participants accessed on their own time. However, the authors suggest that the findings may inform patients’ and doctors’ conversations about whether or not to use cannabis.
National Academy of Sciences, Engineering and Medicine Issues Report on the Health Effects of Cannabis
In early 2017, the National Academy of Sciences, Engineering, and Medicine issued its first comprehensive report on cannabis since 1999. Shifting public opinion over the past few decades has led to 28 states and the District of Columbia legalizing medical uses of marijuana, and eight states and DC legalizing recreational marijuana use. The Health Effects of Cannabis and Cannabinoids: Current State of Evidence and Recommendations for Research is intended to address the lack of accepted standards to guide individuals in deciding whether and how to use cannabis safely. In addition to summarizing recent health-related findings on cannabis, the report also offers recommendations to guide future research.
The report shares findings about possible therapeutic benefits to cannabis use as well as health impacts relating to areas such as cancer, respiratory disease, immunity, pre- and post-natal health.
There were several notable findings with regard to mental health. The committee that issued the report found substantial evidence of a statistical association between cannabis use and the development of schizophrenia or other psychoses, with the highest risk among the most frequent users.
The committee also found moderate evidence of a link between cannabis use and increased symptoms of mania and hypomania in people with bipolar disorder who use cannabis regularly. The report also describes moderate evidence of an association between heavy cannabis use and increased suicidal ideation and suicide attempts.
There was also moderate evidence that regular cannabis use is linked to social anxiety disorder.
The report described factors that may lead to problem cannabis use. The committee found substantial evidence that being male, smoking cigarettes, and beginning cannabis use at an earlier age are risk factors for developing problem cannabis use. Read more
Early Cannabis Use and BDNF Gene Variant Increase Psychosis Risk
Normal variations in genes can affect risk of mental illness. One gene that has been implicated in psychosis risk is known as BDNF. It controls production of brain-derived neurotrophic factor, a protein that protects neurons and is important for learning and memory. Another important gene is COMT, which controls production of the enzyme catechol-O-methyltransferase, which breaks down neurotransmitters such as dopamine in the brain.
Several forms of these genes appear in the population. These normal variations in genes are known as polymorphisms. Certain polymorphisms have been linked to disease risk. A study by Anna Mané and colleagues published in the Journal of Psychiatric Research in 2017 explored links between COMT and BDNF polymorphisms, cannabis use, and age at first episode of psychosis.
Mané and colleagues found that among 260 Caucasians being treated for a first episode of psychosis, the presence of a BDNF polymorphism known as val-66-met and a history of early cannabis use were associated with younger age at psychosis onset.
The val-66-met version of BDNF occurs in 25-35% of the population. It functions less efficiently than a version called val-66-val.
The researchers also found that males were more likely to have used cannabis at a young age.
Editor’s Note: In the general population, marijuana use doubles the risk of developing psychosis. Previous data had indicated that the risk was higher for those with a COMT polymorphism known as val-158-val that leads to more efficient metabolism of dopamine in the prefrontal cortex. The resulting deficits in dopamine increase vulnerability to psychosis compared to people with the val-158-met version of the COMT gene.
The new study by Mané and colleagues suggests that a common form of BDNF may be associated with an earlier onset of psychosis. Bottom line: Pot is dangerous for young users and can induce psychosis, particularly in people at genetic risk. Pot may be legal in many places, but heavy use in young people remains risky for mental health and cognitive functioning.
The company Genomind offers genetic testing for BDNF and COMT variants as part of a routine panel.
Cannabis Use May Cause Schizophrenia
Cannabis use has been linked to schizophrenia risk, and new genetic research suggests a causal relationship between the two. In a 2017 article in the journal Molecular Psychiatry, researcher Julian Vaucher and colleagues reported that lifetime cannabis use was linked to schizophrenia even when the researchers controlled for 10 genotypes weakly associated with lifetime cannabis use. This makes it unlikely that the schizophrenia caused the cannabis use, suggesting instead that it is the cannabis use that leads to a schizophrenia diagnosis.
Vaucher and colleageus also controlled for genetic associations between cigarette smoking and cannabis use to eliminate cigarette use as a third variable causing the association between cannabis and schizophrenia.
The study by Vaucher and colleagues included 34,241 people with schizophrenia and 45,604 healthy controls.
Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients
M M Bergamaschi, et al reported in Neuropsychopharmacology volume 36, pages 1219–1226 (2011) that the one of the ingredient in cannabis, the diol or cannabidiol (CBD), containing none of the usual THC which make up the vast majority of plant-based marijuana, reduces the anxiety Induced by simulated public speaking in treatment-naïve social phobia patients. They used “CBD (600?mg) in powder, ?99.9% pure (kindly supplied by STI-Pharm, Brentwood, UK and THC-Pharm, Frankfurt, Germany),… dissolved in corn oil.” This CBD has shown efficacy in other anxiety disorders and is FDA approved for one form of seizure disorder. This pure form of CBD is very expensive and usual preparations of available cannabis contain mostly THC and only minute amounts of CBD. Thus, the generalizability of these results to people using the widely available preparations of cannabis is extremely unlikely.
Environment Can Leave “Molecular Scars” Via Epigenetic Processes
A 2020 review article by researchers Julia Richetto and Urs Meyer in the journal Biological Psychiatry provides a good overview of the role epigenetic modifications play in schizophrenia and related disorders.
The article provides a powerful understanding of how the environment can induce long-lasting changes in the structure of DNA (not only in schizophrenia, but also in bipolar disorder). This process, known as epigenetics, can have life-long influences on brain chemistry and behavior, and remarkably, some of these epigenetic changes can even be transmitted to the next generation.
While the sequence of DNA that one inherits from one’s parents does not change over the course of one’s life, what can change is how loosely or tightly the DNA is wound around proteins called histones, making it easier or harder to transcribe the genetic material held there. The addition of a methyl group to DNA usually inhibits transcription, while the addition of an acetyl group to histones usually facilitates transcription. These alterations in the shape of the DNA that result from environmental exposures or behavior can be passed on through generations.
Richetto and Meyer describe these chemical changes to DNA as “molecular scars,” which are left when environmental stress occurs during sensitive developmental periods. For example, patients with schizophrenia who experienced stressors in early life have higher levels of the enzyme histone deacetylase than patients who had stress or trauma later in life. Histone deacetylase would remove the acetyl groups on histones, which would inhibit gene transcription.
Other factors that have been implicated in epigenetic modifications in schizophrenia, such as DNA methylation of key developmental pathways, include pre- or post-natal stress, a challenge to a mother’s immune system during pregnancy, pre- and post-natal nutrition, exposure to drugs or toxic substances, and cannabis use in adolescence.
Richetto and Meyer suggest that epigenetics may explain why schizophrenia (and we would add bipolar disorder) can differ so much across individuals, and may help researchers and clinicians determine how best to treat different individuals.
Editor’s Note: This editor has written about how epigenetic changes can mediate sensitization to the recurrence of life stressors, episodes of mood disorder, and bouts of substance abuse, each of which can drive illness exacerbation and progression in bipolar disorder (see the 2016 article by Robert M. Post in the journal Bipolar Disorders, “Epigenetic basis of sensitization to stress, affective episodes, and stimulants: implications for illness progression and prevention”).
The chemical changes to our DNA, histones, and microRNA emphasize how important it is to begin long-term preventative treatment starting after a first episode of mania. This not only helps limit episode recurrence and the accumulation of stressors and bouts of substance use that can cause illness deterioration, but also limit the placement of these “molecular scars” on our DNA. The key to treating bipolar disorder is: prevent episodes, protect the person and the brain.
