Continuing Marijuana Use After a First Episode of Psychosis Increases Risk of Relapse

May 5, 2017 · Posted in Risk Factors · Comment 

marijuanaA 2016 article in the journal JAMA Psychiatry reports that continuing to use cannabis after a first episode of psychosis increases risk of relapse. The study by Sagnik Bhattacharyya and colleagues employed longitudinal modeling to determine the role of cannabis use in psychotic relapse. The researchers followed 90 women and 130 men for two years after a first episode of psychosis, and found that the more marijuana they used, the more likely they were to have a relapse of psychosis.

Relapse rates were highest (59.1%) for participants who used pot continuously following their first episode of psychosis. Relapse rates were lower (36.0%) for those who used cannabis intermittently thereafter, and lowest (28.5%) among those who discontinued cannabis use after their first episode of psychosis.

A statistical test known as a cross-lagged analysis was used to establish that cannabis use affected later relapse, rather than relapse of psychosis leading to further cannabis use.

Another statistical strategy using fixed-effect models revealed that risk of psychotic relapse was 13% higher during times of cannabis use than during periods of no cannabis use.

These findings offer some hope that the likelihood of psychosis relapse can be reduced, since ongoing cannabis use is a risk factor that can be modified, unlike family history or genetics. Bhattacharyya and colleagues called for research into interventions that can help discourage cannabis use in people who have had a first episode of psychosis.

Editor’s Note: N-acetylcysteine, a nutritional supplement sold in health food stores, can reduce cannabis use compared to placebo in teen users.

Early Cannabis Use and BDNF Gene Variant Increase Psychosis Risk

May 3, 2017 · Posted in Genetics, Risk Factors · Comment 

Teen smoking marijuanaNormal 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

May 1, 2017 · Posted in Risk Factors · Comment 

marijuanaCannabis 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.

Topiramate Added to Quetiapine Can Reduce Marijuana Craving in Young People

February 11, 2016 · Posted in Current Treatments · Comment 

marijuana craving

At the 2015 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Melissa P. DelBello reported that compared to placebo, the anticonvulsant topiramate reduced marijuana craving in young people aged 12–21 who were already taking the antipsychotic quetiapine. Functional magnetic resonance imaging (fMRI) revealed that topiramate altered the activation of brain regions common to both drug craving and mood dysregulation. Topiramate could be a good treatment to reduce marijuana abuse. The antioxidant n-acetylcysteine (NAC) is another option.

Marijuana Use Worsens PTSD Symptoms in Veterans

January 29, 2016 · Posted in Risk Factors · Comment 

marijuana worsens PTSD symptoms

A 2015 study by Samuel T. Wilkinson and colleagues in the Journal of Clinical Psychiatry reports that among war veterans who completed a special treatment program for post-traumatic stress disorder, those who continued or began using marijuana after treatment had more severe PTSD symptoms, were more violent, and used drugs and alcohol more often. Those who stopped using marijuana or never used it had the lowest levels of PTSD symptoms in the study.

Editor’s Note: Scientific information about marijuana is almost never reported in the media. Evidence of the adverse effects of heavy marijuana use are robust and consistent.

Some of these include:

  • A doubling of the risk of psychosis compared to non-users. People with a common variation in the enzyme COMT, which metabolizes dopamine, have an even higher rate of psychosis.
  • An increased risk of bipolar disorder onset.
  • A worse course of bipolar disorder.
  • An increased risk of schizophrenia.
  • Memory deficits that remain even after marijuana use has ceased.
  • Loss of motivation (exactly what someone with depression doesn’t need).
  • Anatomical changes in brain structures.
  • A worse course of PTSD and increased violence in those with PTSD.

Bottom line: Those who say marijuana is benign may be ill-informed. People with mood disorders, proneness to paranoia, or PTSD should stay away from marijuana.

Marijuana May Speed Cortical Loss in Boys at Risk for Schizophrenia

January 28, 2016 · Posted in Risk Factors · Comment 

marijuana

In boys, a decrease in the thickness of the cortex is a part of normal maturation. However, according to a recent study, this process is sped up in boys at high risk for schizophrenia when they use marijuana before the age of 16.

Early use of marijuana has been linked to subsequent development of schizophrenia. Schizophrenia begins about 5 years earlier in males than in females, and the male brain goes through more structural changes during adolescence.

A 2015 article by Tomáš Paus in the journal JAMA Psychiatry incorporated data from three studies, which took place in parts of Canada and England and eight European cities. The studies all included magnetic resonance imaging (MRI) scans of the participants, a measure of their genetic risk of developing schizophrenia, and questions about their past marijuana use. In boys at high risk for schizophrenia based on their genetic profile, cortical thickness dropped more among the ones who used high amounts of marijuana before the age of 16 compared to those who did not.

Paus hypothesizes that the development of schizophrenia is a “two-hit process.” People who develop schizophrenia may have an early risk factor, such as their genetic profile or a problem that occurs in utero, and a later stressor such as drug use in adolescence.

Link Between Childhood Trauma and Difficult Course of Bipolar Disorder Clarified

November 9, 2015 · Posted in Genetics, Risk Factors · Comment 

Trauma in childhood linked to course of bipolar disorder

A collaboration between Norwegian and French researchers led by Bruno Etain has clarified the pathway by which childhood trauma is linked to worse outcomes among people with bipolar disorder. The researchers, who presented their work in a poster at the 2015 meeting of the Society of Biological Psychiatry, replicated earlier findings by this editor (Robert Post) that patients who experienced trauma as a child had a more adverse course of bipolar disorder. Etain and colleagues found a link between childhood trauma and an earlier age of onset of bipolar disorder, rapid cycling, suicide attempts, and cannabis misuse.

The researchers identified more than 550 patients with bipolar disorder, who answered questionnaires about their history of bipolar disorder and childhood trauma. Their DNA was also analyzed, and the researchers found that the effect of childhood trauma on age of onset was mediated by the presence of common genetic variants in proteins related to stress (the serotonin transporter) and immune function (Toll-like receptors). They also found that the traits of mood lability (or moodiness) and impulsivity mediated the effects of trauma on clinical outcomes.

The lasting epigenetic effects of child maltreatment and adversity noted in the above abstract are consistent with a large literature showing more epigenetic effects in these individuals than in controls. While genetics are important, the impact of the environment is also substantial.

Halting Marijuana Use Might Improve Memory

November 19, 2014 · Posted in Risk Factors · Comment 

teen smoking a joint

Researcher Amanda Roten reported at the 2014 meeting of the American Academy of Child and Adolescent Psychiatry that adolescents who stopped heavy marijuana use showed improvements in multiple areas of learning and memory. These data support previous findings that pot can cause impairments in cognitive functioning, but that abstaining from the drug can bring about improvement relative quickly.

These data contrast with some others. A 2009 study by J. Jacobus et al. in the journal Pharmacology Biochemistry and Behavior suggested that some changes in brain structure resulting from marijuana use, such as decreases in cortical volume, can persist for one to three months following abstinence.

Madeline Meier, another researcher at the meeting, reported that 1,037 participants who used marijuana persistently from about age 13 to age 38 lost an average of 8 IQ points. Controlling for years of education and other potential confounds such as alcohol and drug use did not affect these findings. Moreover, Meier found that “cessation of cannabis use did not fully restore IQ among adolescent-onset cannabis users.”

Editor’s Note: The popular view that marijuana is a benign substance overlooks some key facts. The main pharmacological effect of pot is an amotivational syndrome, causing apathy and lack of drive to participate in work, study, and other activities. Heavy use of pot doubles the risk of psychosis, and this risk is further increased if a user has a common genetic variation in the enzyme catechol-o-methlyl transferase (COMT), which metabolizes dopamine. The more efficient allele of COMT (known as val-56-val, identifying two valine amino acids) lowers frontal cortex dopamine more, and increases the risk of delusions and hallucinations. Marijuana alters brain structure and impairs memory. It may now be legal in some states, and while reducing penalties for smoking marijuana may be a good idea, this does not mean the drug is a harmless substance.

The moral of the story is that avoiding marijuana use in the first place, especially for people with bipolar disorder, should make it easier to get well and stay well. For current marijuana users, N-acetylcysteine (NAC, a nutritional supplement available without a prescription from health food stores) has been shown to help adolescents decrease marijuana use more than placebo.

How the Chemicals in Marijuana Work in the Brain

October 9, 2014 · Posted in Neurochemistry · Comment 

marijuana

Raphael Mechoulam, who first synthesized THC, the main ingredient in marijuana, gave the history of marijuana and its receptors in the central nervous system in a plenary talk at the 2014 meeting of the International College of Neuropsychopharmacology. In Syria hundreds of years ago the drug was named ganzigunnu, meaning “the drug that takes away the mind.” It has also been called azalla, meaning “hand of the ghost.” Among the 100 compounds in marijuana, the best-known ingredient is delta-9-tetrahydrocannabinol (delta-9 THC), which produces most of the actions of the drug. There is another active ingredient, cannabidiol (CBD), which has calming and anti-anxiety effects, but is present in very low levels.

The brain has cannabinoid receptors that respond to ingredients in marijuana in addition to other chemicals produced in the brain. They modulate calcium ions and decrease the release of many neurotransmitters.

THC acts at CB-1 receptors, producing the high. The CB-1 receptor is synthesized on demand, post-synaptically, and is transferred to the pre-synaptic terminal where it decreases calcium and transmitter release. Consistent with marijuana’s appetite-stimulating properties (“the munchies”), if the CB-1 receptor is blocked in animals, they lose their appetite and die of hunger.

There are also low levels of CB-2 receptors in the brain, whose activation does not cause a high, and whose levels may increase dramatically in pathological situations. Activation of the CB-2 receptor is anti-inflammatory and, in the same way that the immune system acts against foreign proteins, CB-2 acts as a protector against non-proteins.

CBD does not bind to any cannabinoid receptors, but its actions are blocked by cannabinoid antagonists.

There are two chemicals in the brain (endogenous ligands) that act at cannabinoid receptors—anandamide and 2-arachidonoylglycerol (2-AG). They are soluble only in lipids (not in water), and have never been given to people. In animals, 2-AG has neuroprotective effects, decreases the size of a stroke by 60%, and increases recovery from stroke.

Marijuana and CBD in particular have also had beneficial effects in people. Marijuana decreases the nausea and vomiting associated with chemotherapy in children, has anti-inflammatory effects in rheumatoid arthritis (decreasing inflammatory marker TNF alpha), and has anti-diabetes and anti-convulsant effects.

In 2012, researcher F. Markus Leweke and colleagues showed that CBD was about as effective as the atypical antipsychotic amisulpiride in alleviating the psychotic symptoms of schizophrenia. CBD’s other effects include reducing anxiety and improving psoriasis by increasing DNA methylation (Pucci et al. 2013).

It seems possible that some of these myriad effects of marijuana and endogenous ligands at CB receptors could be exploited for clinical therapeutics, as Mechoulam endorses, but when and how that will take place remains an unanswered question.

Editor’s Note:  Despite all these potential positives of CBD, it should be noted that its levels are very low in marijuana, and that heavy smoking of marijuana has substantial adverse effects. These include low motivation, a doubling of the risk of psychosis, a hastening of the onset of bipolar disorder and schizophrenia, and cognitive impairment, as well as some changes in brain structure seen via magnetic resonance imaging (MRI). It may be becoming legal in many states, but is a bad idea for those at high risk for mood, anxiety, or bipolar disorders or for schizophrenia.

Marijuana Addiction Associated with White Matter Loss and Brain Changes in Healthy People and Those with Schizophrenia

March 5, 2014 · Posted in Risk Factors · Comment 
white matter

In an image from an MRI, the blue color depicts low blood volume, indicating areas of white matter.

It has been established that cannabis use is associated with impairments in working memory, but researchers are still investigating how these impairments come about. A 2013 study by Matthew J. Smith et al. in the journal Schizophrenia Bulletin compared regular marijuana users both with and without schizophrenia with demographically similar people who did not use marijuana.

Using magnetic resonance imaging (MRI), the researchers were able to map each participant’s brain structures. Healthy people who were marijuana users showed deficits in white matter (axons of neurons that are wrapped in myelin) compared to healthy people who did not use the drug. Similarly, patients with schizophrenia who used marijuana regularly had less white matter than those patients with schizophrenia who did not use the drug. There were also differences in the shapes of brain structures, including the striatum, the globus pallidus, and the thalamus, between cannabis users and non-users.

Differences in the thalamus and striatum were linked to white matter deficits and to younger age of cannabis use disorder onset.

Differences between cannabis users and non-users were more dramatic across the populations with schizophrenia than across the healthy populations.

Editors note: Future research is needed to determine whether marijuana causes these brain changes, or whether the brain changes are a biomarker that shows a vulnerability to marijuana addiction (although the latter is less likely than the former).

Other data show that marijuana is associated with an increase in psychosis (with heavy use), cognitive deficits, and an earlier onset of both bipolar disorder and schizophrenia in users compared to non-users. These findings make pot begin to look like a real health hazard. With legalization of marijuana occurring in many states, ease of access will increase, possibly accompanied by more heavy use. The most consistent pharmacological effect of marijuana is to produce an amotivational syndrome, characterized by apathy or lack of interest in social activities. Particularly for those already struggling with depression, pot is not as benign a substance as it is often thought to be.

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