While there are strong links between excessive usage of THC, especially in adolescents, with triggering psychosis and schizophrenia, CBD has been found to have the opposite effect. Can you successfully use cannabis, particularly the non-intoxicating CBD, to treat schizophrenia? Does THC actually cause the condition? Prepare for several mind-blowing facts about CBD, cannabis, and schizophrenia. Clinical research shows CBD is as effective as antipsychotic meds with fewer side effects.
CBD Fights Schizophrenia, but with Different Dose Range for Different Symptoms
In journalism and media industry for more than twenty years, worked for a number of media companies. Business editing, research and PR specialist. Covering industry and science news for Ilesol Pharmaceuticals.
CBD Fights Schizophrenia, but with Different Dose Range for Different Symptoms
Have you wondered about CBD and its effect in treating schizophrenia? Schizophrenia is a chronic and in many cases permanently disabling mental disorder that affects about one percent of the world’s population. According to the World Health Organization, more than 26,3 million people suffer from the disease, 16,7 million are disabled and it is accounted for 30.000 fatal outcomes a year, half of which take place in South East Asia.
Schizophrenia is characterized by episodes of psychosis between periods of a blunted emotional state and stupor. Symptoms that occur during episodes of psychosis are called ‘positive symptoms’ and include impaired mental activity, a delirium that consists of false beliefs, and is often accompanied by paranoia; and hallucinations, most commonly in the form of hearing prying voices. These symptoms are accompanied by anxiety, depression, and excessive activity, e.g. constant movement and agitation.
Negative symptoms of schizophrenia include blunted emotions, a decrease in the frequency of speech, a deterioration in the ability to plan, start or continue any activity, and a reduction in the perception of positive emotions or interest. These symptoms can cause severe problems in social interaction and daily life.
The third group – cognitive symptoms of schizophrenia include disorganized thinking, slow thinking, difficulty understanding, poor concentration, poor memory, difficulty expressing thoughts, and difficulty integrating thoughts, feelings, and behavior.
The opposite effects of THC and CBD
While there are strong links between excessive usage of THC, especially in adolescents, with triggering psychosis and schizophrenia, CBD has been found to have the opposite effect . Nonetheless, a significant proportion of patients don’t respond to traditional antipsychotics , that only target the positive symptoms, with little effect on negative or cognitive symptoms. On top of that, dopamine-acting antipsychotics are associated with a number of side effects, some of which can be severe.
These understandings have driven the attention of scientists to provide more scientific evidence on the effects of CBD on patients who suffer from schizophrenia.
In 1982, a study of the interactions between THC and CBD in healthy volunteers provided the first evidence that CBD might have antipsychotic properties. This finding was confirmed in 1995 when a study published in the Journal of Clinical Psychiatry concluded that CBD has an atypical antipsychotic profile.
Lately, in 2018, at the South London and Maudsley NHS Foundation Trust in London, United Kingdom, a clinical trial was conducted where 33 antipsychotic medication–naive participants at clinical high risk of psychosis and 19 healthy control participants were studied. The scientists used functional magnetic resonance imaging to inspect the effects of CBD on parahippocampal, striatal, and midbrain function – the three brain functions active in schizophrenia. Observing the level of activation in the left parahippocampal brain cortex, the study concluded that a single dose of CBD may partially normalize dysfunction in the medial temporal lobe, striatum, and midbrain in the individuals at clinical high risk of psychosis.
Very recently, in May this year, Antonio Waldo Zuardi an d José Alexandre Crippa from the University of São Paulo published an article in the Psychiatric Times, where they discuss the current stage of scientific evidence that supports the use of cannabidiol in schizophrenia, anxiety, and Parkinson disease.
The article underlines the connection between cannabis and psychosis as having a centuries-long history, that goes back to 2700 BC, when Shen-nung pen ts’ao ching ( Divine Husbandman’s Materia Medica ) , the world’s oldest pharmacopeia attributed to Chinese emperor Shen-Nung, stated that “. . . ma-fen (the fruit of cannabis), if taken in excess, will produce visions of devils . . . over the long term, it makes one communicate with spirits.”
In the 19th century, French psychiatris t Jacques-Joseph Moreau started using cannabis as an experimental psychotomimetic, a drug that mimics the symptoms of psychosis, and, apparently, it’s been used for that purpose in Western medicine to this day. Consistent scientific evidence indicates that the chronic and intense use of the plant, especially if started in adolescence, contributes to the occurrence of schizophrenia.
Great results with intermediate doses of CBD in schizophrenia
After the study in 1982, which provided the first evidence that CBD might have antipsychotic properties, the same observation was confirmed in a study with THC administrated intravenously after oral pretreatment with CBD or placebo. In addition to blocking the psychotic symptoms induced by THC, CBD and THC demonstrated opposite effects.
This led the scientists to carry out a pioneering study to test the effects of CBD on laboratory animals. The stereotypy induced in rats was clearly reduced by CBD, without producing catalepsy, the study has found. The next step was to evaluate the effects of CBD in a patient with schizophrenia. The patient was a chronically psychotic young female who has experienced many adverse effects from traditional antipsychotics, which presented the ethical justification for the first clinical test. After four weeks of treatment, the patient had a marked reduction in her psychotic symptoms.
The patient was given up to 1500 mg per day in two divided doses, with weekly reducing diazepam dose, which was being given for periods of great agitation and anxiety. The dose of diazepam was reduced from 16,3 to 5,7 mg per day. The improvements of her condition were observed in all the symptoms closely related to the psychosis, including thought disturbance and hostility-suspiciousness.
To date, three randomized controlled trials have evaluated the therapeutic effects of CBD in schizophrenia patients. The first one included 39 patients treated with either CBD (800 mg/d; n = 20) or the atypical antipsychotic amisulpride (800 mg/d; n = 19) for four weeks. Both drugs led to a similar significant reduction in both positive and negative psychotic symptoms, but fewer adverse effects were seen in the CBD group.
In the other two trials, the results were contradictory. Treatment with a dose of 1000 mg per day significantly reduced positive symptoms , while the other study with 600 mg per day found no significant symptomatic differences between CBD and placebo. It is possible that the explanation for the contradictory results lays in the difference in CBD doses.
The CBD dose-response relationship appears to have a particular feature, Zuardi and Crippa point out. In 1990, CBD was tested in a range of doses in rats with the elevated plus-maze model and was found to act according to a bell-shaped dose-response curve. CBD induced an anxiolytic-like effect only at intermediate doses. At a dose of 20,0 mg/kg, it was no longer effective.
The dose-response curve was also observed in healthy volunteers subjected to anxiety induced by the simulation of public speaking test and by public speaking in real settings. In the first situation, volunteers were asked to speak for a few minutes in front of a video camera, while in the second each subject had to speak in front of a group of other research participants. In both situations, treatment with CBD 300 mg was associated with significant decreases in anxiety symptoms, but this effect was not observed with lower or higher doses.
Zuardi and Crippa observed the same response pattern in preclinical tests using other models of induce d anxiety, cognitive impairment, and schizophrenia-like behavior. The findings suggest that this inverted U-shaped curve response pattern may be extended to other therapeutic effects of CBD, with different effective doses and therapeutic windows for each condition.
The data from all three studies in schizophrenia patients suggest that the dose range to reduce psychotic symptoms (probably between 800 and 1000 mg/d), but not cognitive symptoms, should be higher than that used to induce anxiolytic effects (between 200 and 400 mg/d). However, the scientists point out that precise dose ranges for each condition or symptom are yet to be determined.
Reviewed by Sasha Bajilo, founder of ILESOL Pharmaceuticals, an industrial scale producer of CBD products and formulations. Expert on Hemp/Cannabis policy, member of the Croatian Ministry of Health regulatory commission for medical cannabis.
CBD for Schizophrenia: Can Hemp Oil Help with Schizoaffective Disorder?
Although cannabis has got a bad rap when it comes to psychotic disorders such as schizophrenia, the latest research findings indicate that the plant has been largely misunderstood. Studies suggest CBD may actually offset the development of schizophrenia and curb the episodes of psychosis. Better yet, it appears that the other major cannabinoid, THC, may not necessarily trigger the condition — at least not as a direct cause.
Today we’ll focus on the potential CBD treatment for schizophrenia. We’ll cover the recent studies on this subject, explain the mechanism of action, and debunk a few myths about cannabis and mental health.
Using CBD for Schizophrenia: Does It Make Sense?
Cannabis is a complex plant with 115 identified cannabinoids. Depending on the chemotype, cannabis strains may be THC-dominant and CBD-dominant.
Marijuana is known for significant amounts of THC, while hemp boasts higher concentrations of CBD and only traces of the intoxicating cannabinoid.
There are also terpenes, which influence the effect profile of each strain.
The majority of CBD oils available for sale are made from hemp, so their effects revolve around the benefits of CBD supported by other compounds in the plan. A growing body of scientific evidence suggests CBD may relieve anxiety, inflammation and pain, sleep disturbances, and balance mood.
The FDA has recently approved the first cannabis plant-derived medication, Epidiolex. It contains pure CBD and is recommended for treatment-resistant seizures. However, doctors may prescribe Epidiolex off-label for other conditions, such as schizophrenia.
What to Know About CBD and Schizophrenia?
There is a clear link between cannabis use and psychosis, as noted by epidemiological studies. However, a higher risk of schizophrenia has been associated with strains that have high THC content, and studies have notoriously mentioned a dose-response relationship for the risk of schizophrenia in cannabis users. This isn’t the case for high-CBD strains.
THC produces acute psychotic-like symptoms in healthy individuals after a certain dosage threshold is breached — but CBD decreases the THC-induced psychosis and cognitive impairment.
Patients with schizophrenia suffer from cognitive deficits — they affect up to 85% of the sufferers, so the potential positive effects of CBD on cognition have critical importance.
Below we shed more light on how CBD may help with schizophrenia.
Antipsychotic Properties of CBD
A case study published by Zuardi and colleagues found that CBD may successfully treat schizophrenia. The authors tested a dose of CBD up to 1500 mg daily for 4 weeks, which improved the acute psychotic symptoms (1).
Findings from a 2006 study that analyzed the efficacy of CBD as monotherapy for treatment-resistant schizophrenia in three individuals show that only one patient responded positively to the treatment, but the dosage might’ve been inadequate (2). A later study on the benefits of CBD for schizophrenia tested flexible doses up to 400 mg daily on 6 patients with Parkinson’s disease, finding improvement of psychotic symptoms in all participants over the course of 4 weeks.
Since then, CBD has been investigated for its antipsychotic properties in three clinical studies with contradictory results.
For example, a 2012 double-blind randomized controlled trial on the therapeutic effects of CBD showed that the cannabinoid was as effective as amisulpride, a common antipsychotic drug, in treating the symptoms of schizophrenia. On top of that, CBD had fewer side effects; it caused no weight gain and resulted in less extrapyramidal symptoms (4).
CBD was also tested as an adjunctive medication in the treatment of acute psychosis in people with schizophrenia and non-affective psychotic disorders. After 6 weeks of taking 1000 mg of CBD daily, the CBD group showed greater improvement of positive psychotic symptoms compared to the placebo group. At the end of their therapy, more patients in the CBD group were evaluated as “improved” on the CGI-I scale compared with the controls. Patients who took CBD also showed trend-level improvements in their cognitive performance and motor speed (5).
A similar 2018 study investigated the therapeutic effects of 600 mg CBD daily — divided into two doses — in comparison with placebo in a 6-week double-blind placebo-controlled randomized clinical trial. However, the lower dose didn’t have a significant impact on the psychotic symptoms and cognitive performance of the participants compared to the placebo group (6).
How Does CBD Work for Schizophrenia?
Despite being supported by several epidemiological and clinical studies, the mechanism of action behind the antipsychotic properties of CBD remains unknown. Unlike other antipsychotics, CBD doesn’t directly affect dopaminergic neurons. It also doesn’t bind to cannabinoid receptors like THC.
However, CBD does indirectly increase the CSF levels of anandamide, one of the main endocannabinoids, by blocking its metabolizing enzyme, fatty acid amine hydrolase (FAAH). Interestingly, anandamide levels show a negative correlation with the severity of psychotic symptoms, whereas increased levels of anandamide have been found to improve them clinically after a CBD treatment.
This may hint to CBD as the potential mediator in the management of psychosis through the aforementioned boost of the endogenous levels of anandamide. However, further research is needed to confirm this theory.
Over the past few decades, medical researchers have been exploring the endocannabinoid system as the potential therapeutic target for mental disorders (7). The current pharmacological treatment for schizophrenia is only partially effective and doesn’t tackle the negative symptoms. This has led scientists to search for new pharmacological targets — and the findings from the ECS studies are very promising.
However, there’s a discrepancy in clinical results regarding CBD’s efficacy in treating schizophrenia and psychotic episodes. They could stem from different doses of CBD, stages of psychosis, and heterogeneity of the condition.
Risk and Side Effects: Can CBD Cause Psychosis?
There’s currently no evidence that CBD can cause psychosis. In order to do that, the cannabinoid would have to induce intoxication, elevating anxiety, and paranoia in the dose-response pattern. CBD has been repeatedly shown to reduce anxiety, help with the symptoms of PTSD, addiction, and improve people’s response to stress. CBD has a balancing effect on the nervous system, reducing the hyperactivity and increasing the hypoactivity of neurotransmitters when needed.
CBD is a safe substance. Studies have tested doses as high as 1,500 mg daily without dangerous side effects. That being said, there are a few mild reactions you may experience when you take too much CBD at a time:
- Changes in appetite
- Dry mouth
There’s also a risk of CBD-drug interactions, so make sure to consult your doctor prior to buying CBD oil if you want to avoid them.
The relationship between cannabis use and schizophrenia refers to how THC affects the brain.
But are you sure you have been taught the truth? Let’s take a brief look at the effects of THC on people predisposed to schizophrenia.
Does THC Cause Schizophrenia?
THC is an anti-inflammatory compound with antidepressant-like properties. In low and moderate doses, it also has a relaxing effect on top of inducing an altered state of mind, such as euphoric mood, giggles, and tranquility. However, doses of THC that score higher than your tolerance may aggravate anxiety and trigger bouts of paranoia, especially in those who are sensitive.
Studies conducted in the past have shown a correlation between cannabis use and a faster onset of schizophrenia in people with a family history of the condition. However, the conclusion might have been too hasty, as the latest research shows.
A study performed by Harvard University has analyzed all contributing factors besides cannabis use, pointing to the hereditary burden as the main trigger of schizophrenia in cannabis users. According to the research team, cannabis can only spur the onset of schizophrenia, but it’s not a trigger per se.
In other words, if a person is predestined to have schizophrenia, they will develop it sooner or later.
According to Dr. Musa Sami, a researcher and psychiatrist from King’s College in London increased cannabis use would need to positively correlate with the severity of psychosis, which hasn’t been proven by any study to this day.
Finally, Italian scientists from the University of Calgary have recently tested whether cannabis use will further harm the brain structure of rats that were prenatally exposed to an inflammatory agent that disrupts dopamine signaling and causes behavioral symptoms of schizophrenia. To their surprise, exposure to THC during adolescence seemed to protect the rats’ brains. The authors of the study hypothesized that THC’s anti-inflammatory effects were responsible for offsetting schizophrenia (8).
How Much CBD to Take for Schizophrenia?
The studies we’ve covered above have tested how pure CBD affects the mental health of the participants. However, most people use full-spectrum CBD products, where CBD is only one of over 400 compounds. These compounds influence the way CBD affects the body and brain, so doses may vary between people. Whole-plant extracts require a lower dose than CBD isolates, for which most studies have used a daily dose of 600 to 1,000 milligrams.
If you’re using a full-spectrum or broad-spectrum CBD oil, it’s best to start with a low dose, say, 15 mg once or twice a day with food. If you don’t feel a difference in your symptoms after one week, increase by 10–15 mg and reassess the effects. Once you’ve found your optimal dosage, you can stick to it — there’s no risk of increasing your tolerance to CBD over time.
Do Your Research Before Buying CBD for Schizophrenia
The CBD market is regulated due to the current classification of hemp-derived products. As health supplements, CBD extracts aren’t subject to any standardization when it comes to quality and labeling. Although the market has positively evolved over the years, there are still many fly-by-night vendors churning out poor quality products with less CBD than advertised. Some of them may contain more than 0.3% THC; others may be contaminated with pesticides, solvent residue, and other impurities.
For this reason, you should always check how the company grows, tests, and processes its CBD products.
The best source of CBD is organically grown hemp. Hemp plants are dynamic bio accumulators, so they easily absorb everything from the environment they grow in. Organic farming ensures that you only get the good substances in the source material.
Another important factor on your checklist should be the extraction method. Premium-quality CBD oils are extracted using pressurized CO2; this method produces pure extracts with consistent potency throughout the batches. It doesn’t use additional heat or solvents, so you’re getting a product with a complete cannabinoid profile.
Last but not least, look for certificates of analysis or COA. This shows that each batch is tested by a third-party laboratory. Independent laboratories analyze the potency of the product and look for common contaminants, such as heavy metals, pesticides, or solvent residue.
Summarizing the use of CBD for Schizophrenia
CBD can be used to manage schizophrenia thanks to its therapeutic effects on psychotic symptoms. It may also have a role in preventing or treating cannabis-induced psychosis in vulnerable individuals who consume high-THC strains.
High CBD content may positively affect our mental health — not only by curbing psychosis but also by reducing anxiety and improving the body’s response to stress. Studies investigating the efficacy of CBD in mental disorders have found that the cannabinoid has a calming effect on the nervous system but without the dangerous side effects of commonly prescribed antipsychotic medications.
Clinical trials on CBD and schizophrenia have brought mixed results, most likely due to the discrepancy in dosages. If you’re considering taking CBD oil to improve the symptoms of your condition, make sure to consult a holistic psychiatrist who will have a good understanding of CBD and cannabis in general. Doing so will help you determine the effective dosage and avoid negative CBD-drug interactions.
- Zuardi, A W et al. “Antipsychotic effect of cannabidiol.” The Journal of clinical psychiatry vol. 56,10 (1995): 485-6.
- Zuardi, Antonio Waldo et al. “Cannabidiol monotherapy for treatment-resistant schizophrenia.” Journal of psychopharmacology (Oxford, England) vol. 20,5 (2006): 683-6. doi:10.1177/0269881106060967
- Zuardi, Antonio Waldo et al. Op. Cit.
- Leweke, F M et al. “Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.” Translational psychiatry vol. 2,3 e94. 20 Mar. 2012, doi:10.1038/tp.2012.15
- McGuire, Philip et al. “Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial.” The American journal of psychiatry vol. 175,3 (2018): 225-231. doi:10.1176/appi.ajp.2017.17030325
- Boggs, Douglas L et al. “The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo-controlled trial.” Psychopharmacology vol. 235,7 (2018): 1923-1932. doi:10.1007/s00213-018-4885-9
- Leweke, F Markus et al. “Role of the Endocannabinoid System in the Pathophysiology of Schizophrenia: Implications for Pharmacological Intervention.” CNS drugs vol. 32,7 (2018): 605-619. doi:10.1007/s40263-018-0539-z
- Lecca, Salvatore et al. “Δ9-Tetrahydrocannabinol During Adolescence Attenuates Disruption of Dopamine Function Induced in Rats by Maternal Immune Activation.” Frontiers in behavioral neuroscience vol. 13 202. 6 Sep. 2019, doi:10.3389/fnbeh.2019.00202
Livvy is a registered nurse (RN) and board-certified nurse midwife (CNM) in the state of New Jersey. After giving birth to her newborn daughter, Livvy stepped down from her full-time position at the Children’s Hospital of New Jersey. This gave her the opportunity to spend more time writing articles on all topics related to pregnancy and prenatal care.
CBD for Schizophrenia
Schizophrenia is a mental disorder that affects a person’s ability to think, feel, and behave clearly. It can cause psychotic episodes, and treatment is usually lifelong and involves antipsychotic medications with toxic side effects.
In 2012, researchers published a study in Translational Psychiatry showing that a CBD isolate can treat schizophrenia as effectively as antipsychotic pharmaceuticals — and with far fewer side effects. 1
In this study, researchers led by Markus Leweke, MD , of the University of Cologne in Germany recruited 39 people with schizophrenia who were hospitalized for a psychotic episode. Nineteen of the study participants received an antipsychotic medication called amisulpride, while the other 20 were given CBD . After four weeks, both groups significantly improved. There was no difference in psychiatric symptoms between those getting CBD or amisulpride. But those taking CBD had fewer undesirable side effects, such as weight gain and movement disorders, compared to those taking amisulpride. The authors concluded, “These results suggest that cannabidiol is as effective at improving psychotic symptoms as the standard antipsychotic amisulpride.”
CBD appears to provide antipsychotic relief by raising the levels of anandamide, an endogenous cannabinoid compound that acts on the same brain receptors as THC . Curiously, in an earlier study, Daniele Piomelli, director of the Center for the Study of Cannabis at the University of California in Irvine, discovered that people with schizophrenia had anandamide levels that were on average twice as high as mentally healthy people without the disorder. 2 Some scientists speculated that perhaps people with schizophrenia were essentially too high on elevated levels of their own endocannabinoids! But in reality, it seems that the brain actually increases anandamide levels to buffer stress and ease the symptoms of psychosis. The preponderance of evidence suggests that the higher the anandamide levels are in people with schizophrenia, the less severe their symptoms.
Atypical brain scans
More recently, in 2020, researchers from Kings College in London used fMRI scans to monitor the brain activity of 13 people with psychosis while they performed a memory test after taking CBD or a placebo and compared it to 16 people without psychosis performing the same test. Those taking placebo had different brain activity in the prefrontal and mediotemporal brain areas associated with memory than the people without psychosis. When participants who had psychosis took one dose of CBD , their brain activity becomes more like their counterparts without the disease.
CBD influences areas of the brain that have been shown to have unusual activity in people with psychosis.
“Our study provides important insight into which areas of the brain CBD targets. It is the first time research has scanned the brains of people with a diagnosis of psychosis who have taken CBD and, although the sample is small, the results are compelling in that they demonstrate that CBD influences those very areas of the brain that have been shown to have unusual activity in people with psychosis,” said the senior author on the study, Sagnik Bhattacharyya, MD , PhD. 3
Importantly, in terms of cannabis and safety, one of the biggest health concerns and stigmas about cannabis use has been the idea that it can cause psychosis in vulnerable individuals. This has never been proven. It’s worth noting that a 2012 meta-analysis published in Schizophrenia Bulletin showed that people diagnosed with schizophrenia who use cannabis function better cognitively than people with schizophrenia who do not use cannabis. 4
An excerpt from The Essential Guide to CBD by the editors of Reader’s Digest & Project CBD .
Copyright, Project CBD . May not be reprinted without permission.