Cannabis and Schizophrenia

Cannabis and Schizophrenia

Schizophrenia has only recently been characterized as a metabolic disorder, akin to diabetes. Physicians recognized schizophrenia and its link to other metabolic syndromes as early as the 19^th century, when the doctors noted that diabetes often occurred in families in which insanity was prevalent.
https://www.ncbi.nlm.nih.gov/pubmed/15056595

Cannabis and Schizophrenia History

“Reefer Madness” is a meme supporting the idea that cannabis causes psychosis. It goes back to a popular scare tactic employed by the tabloid press to support the cannabis prohibition efforts of the 1920s and '30s. The link to cannabis and madness originated in the Western Hemisphere with tales of THC-dominant cannabis-induced insanity and violence in Mexican barracks in the 19^th century.
 https://www.jstor.org/stable/10.5149/9780807882689_campos

It was not until the mid - 1990s that Brazilian researchers began to examine the potential for cannabinoids such as CBD for use as antipsychotic medications.
https://www.ncbi.nlm.nih.gov/pubmed/7559378

The link between Cannabis and Schizophrenia

There are several current reviews offering assessments of the possible connections between cannabis and schizophrenia.  
https://www.ncbi.nlm.nih.gov/pubmed/26311150
https://www.ncbi.nlm.nih.gov/pubmed/25912376
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033190/

Higher CBD content of cannabis is linked to a reduction in psychotomimetic effects of cannabis. 
https://www.ncbi.nlm.nih.gov/pubmed/7559378

Some schizophrenic patients claim that cannabis has helped them deal with social rejection, social anxiety, and boredom. They claim not to use cannabis to treat “positive” psychotic symptoms, such as delusions. Cannabis offers a calming and positive socializing effect on its patients. 

One study found evidence for the use of cannabis to treat “positive” symptoms, finding that patients with first-episode psychosis used cannabis to “arrange their thoughts and deal with hallucinations and suspicions.”
https://www.ncbi.nlm.nih.gov/pubmed/26235479

How Cannabis may help Schizophrenia

THC may directly or indirectly contribute to dopamine, GABA, and glutamate dysregulation in areas of the brain linked to the emergence of psychotic symptoms in susceptible patients. The endocannabinoid anandamide activates CB1 receptors in the frontal cortex and hippocampus. By suppressing anandamide’s role in the negative feedback system that normally controls the emergence of psychotic symptoms, THC may dysregulate this natural antipsychotic compensatory system in some susceptible patients.
https://www.ncbi.nlm.nih.gov/pubmed/26311150

A 2015 comprehensive review found that CBD counteracts psychotic symptoms and cognitive impairment associated with THC-dominant cannabis use. CBD lowered the risk for developing psychosis related to cannabis use. Small-scale clinical studies, with CBD treatment of patients exhibiting psychotic symptoms, confirm the potential of CBD as an effective, safe, and well-tolerated antipsychotic compound.
https://www.ncbi.nlm.nih.gov/pubmed/25667194

Pro-psychotic effects of THC were recently thought to be linked to THC’s modulation of dopamine. Recent work indicates these effects may be due to THC’s modulation of gamma-amino butyric acid (GABA; an enzyme that plays a role in behavior and the ways in which the body reacts to stress) and glutamate neurotransmitters.
https://www.ncbi.nlm.nih.gov/pubmed/28185872
https://www.ncbi.nlm.nih.gov/pubmed/26970363
https://www.ncbi.nlm.nih.gov/pubmed/26850792

A randomized-controlled trial (RCT) compared the efficacy of a conventional antipsychotic drug amisulpride with 800 mg of CBD in 39 acutely psychotic schizophrenic patients: both were significantly effective for treatment of “positive” and “negative” symptoms, but CBD caused markedly fewer side effects.
https://www.ncbi.nlm.nih.gov/pubmed/22832859

Both glutamine and dopamine animal models of psychosis have been successfully treated with CBD. A group of researchers conducted a successful study that compared the efficacy of CBD versus an atypical bipolar disorder. CBD was demonstrated in this study to be as effective as the antipsychotic, but with fewer side effects.
https://www.ncbi.nlm.nih.gov/pubmed/16401651

If CBD turns out to be an effective treatment for the negative symptoms of psychosis, combining a high-CBD cannabis treatment with atypical antipsychotics, which are active against “positive” symptoms, may prove to be a significant therapeutic advance in conventional schizophrenia treatments.

At-risk adolescents (victims of neglect or abuse, or who have family history of major psychiatric disorders) should be strongly advised to abstain from high-THC cannabis. However, there is room for clinical judgment. Healthcare professionals and parents of adolescents with severe ADHD, PTSD, inflammatory bowel disease, migraine, or isolating phobias, such as social anxiety, for example, may conclude that the benefits of cannabis outweigh the small risk of cannabis-related psychosis. If cannabis is indicated, then a CBD buffer should be included to mitigate the adverse effects profile of THC.

Although cannabis has been asserted to be a cause of earlier onset of psychosis, detailed studies have shown that the relationship may hold only when cannabis use has begun before the age of 14 and for heavier users; psychotic symptoms do not emerge for six to eight years after first cannabis use is said to have occurred. It is more likely that cannabis use unmasks sub-threshold schizophrenia in previously undiagnosed adolescents.

Abundant evidence points to an association with cannabis use and schizophrenia.
https://www.ncbi.nlm.nih.gov/pubmed/24133460
https://www.ncbi.nlm.nih.gov/pubmed/25912376

The studies apply only to THC-dominant strains of cannabis, and there is a dose dependent relationship. The associations with higher concentrations of THC and heavier cannabis use. None of this evidence applies to high-CBD cannabis. 

A huge twin study, remarkable for its exhaustive statistical analysis, concluded that cannabis use explained only an insignificant 2 – 5 percent variance of psychotic experiences in adolescent twins and that cannabis and schizophrenia are fellow travelers – the guilt is by association, not causation.
https://www.ncbi.nlm.nih.gov/pubmed/25912376

A recent genetic study also concluded that cannabis use predicts only a small amount of the risk for psychosis, and that it is instead due to a shared genetic etiology.
https://www.ncbi.nlm.nih.gov/pubmed/24957864

After the onset of schizophrenia, continued THC-dominant cannabis use has been associated with an increased severity of illness, with worse symptoms, and decreased functioning.
https://www.ncbi.nlm.nih.gov/pubmed/21420282
https://www.ncbi.nlm.nih.gov/pubmed/23590927

Observational studies have found that discontinuing THC-dominant cannabis use improves symptoms, mood, and psychological functioning. 
https://www.ncbi.nlm.nih.gov/pubmed/20478874
https://www.ncbi.nlm.nih.gov/pubmed/23590927

Other studies have found no effect or even improved cognition in the continued-cannabis use group. https://www.ncbi.nlm.nih.gov/pubmed/23884348

There may be a dose effect, in which continuing heavy high-THC cannabis use is associated with worse outcomes – but association must not be interpreted as causation. 
https://academic.oup.com/schizophreniabulletin/article/41/2/382/2526090

Dosing with Cannabis for Schizophrenia

Dose guidance for the use of THC in treating psychosis symptoms must come from a healthcare professional familiar with the patient’s case.

CBD has been shown to relieve anxiety and may hold considerable promise as an antipsychotic. Moderate dosage with CBD is more likely to be considerably safer than THC in treating, but higher doses of CBD can produce mild mental sedation. Treating psychotic symptoms with CBD requires dose guidance from a healthcare professional familiar with the patient’s medical history. Some caution is warranted with high-dose CBD regimens in combination with antipsychotic medications, since CBD may interfere with the metabolism of some drugs.

Smoking or vaporizing cannabis has been popular among schizophrenic patients as a method of self-medication. They typically report using cannabis for mood elevation, relief of social anxiety, or calming of generalized anxiety. If improvements in positive symptoms of schizophrenia is the goal, medical cannabis with a high-CBD content (at least 1:1 or 2:1 CBD:THC) is imperative. 
https://www.ncbi.nlm.nih.gov/pubmed/21592732
https://www.ncbi.nlm.nih.gov/pubmed/18378995

The possibility of drug interactions between medical cannabis and antipsychotic or antidepressant medications is largely unexplored, and should be considered if changes in efficacy of conventional medications are noted.

THC may cause “positive” symptoms in psychosis-prone individuals, and may aggravate “positive” and “negative” symptoms in patients with schizophrenia.
https://www.sciencedirect.com/book/9780124170414/cannabinoids-in-neurologic-and-mental-disease

It is probable that some “negative” symptoms may be improved with medical cannabis.
https://www.ncbi.nlm.nih.gov/pubmed/19752588

The high-ratio CBD:THC phenotypes of cannabis and any similar ultra-high CBD varieties, such as ACDC and Charlotte’s Web, are likely to be the best varieties for most patients attempting to use CBD as an antipsychotic for treatment-resistant schizophrenia. There are a various amount of strains including a high amount of CBD worth looking into and trying.

Information about cannabis and schizophrenia was taken from the amazing medical cannabis book:

Cannabis Pharmacy: The Practical Guide to Medical Marijuana, written by Michael Backes, Andrew Weil, M.D., and Jack McCue, M.D.
You can find this book here

You can find a Medical Marijuana Doctor near you, visit: https://www.marijuanadoctors.com/
You may find chemotypes of cannabis with high CBD ratio at Leafly: https://www.leafly.com/

More information about Cannabis and Schizophrenia can be found at ProjectCBD.org
https://www.projectcbd.org/condition/45/Schizophrenia