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Cbd oil as treatment for psychosis

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.

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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:

  • Dizziness
  • Changes in appetite
  • Dry mouth
  • Diarrhea
  • Fatigue

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.

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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.

Literature:

  1. Zuardi, A W et al. “Antipsychotic effect of cannabidiol.” The Journal of clinical psychiatry vol. 56,10 (1995): 485-6.
  2. 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
  3. Zuardi, Antonio Waldo et al. Op. Cit.
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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 Ashton

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.

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Cannabidiol as an Adjunctive Treatment for Schizophrenia

Cannabis is a complex plant with more than 100 types of cannabinoids. Its main psychoactive compound is δ-9-tetrahydrocannabinol (THC), which activates cannabinoid receptors to produce its “feeling high” effects. Cannabidiol (CBD) is another cannabinoid that has attracted growing attention recently. Unlike THC, CBD does not bind to cannabinoid receptors and has shown different, sometimes counteractive, effects. Currently, there are more than 100 clinical trials registered on the ClinicalTrials.gov website on the potential therapeutic effects of CBD.

The FDA has recently approved the first cannabis plant-derived medication, Epidiolex (an oral solution of pure CBD), for treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients aged 2 years and older. 1 Consequently, DEA scheduled Epidiolex in Schedule V of the Controlled Substances Act (CSA), the least restrictive schedule. 2 Though Epidiolex is only approved for the above rare seizure disorders, physicians may recommend it off-label for other conditions, based on their own judgment. It is important to note, however, that the only approved form of CBD is Epidiolex and off-label recommendation of other forms of CBD does not follow the same rules.

The evidence for cannabidiol

The association between cannabis use and psychosis is well-known in epidemiological studies, and a dose-response relationship is consistently reported with an odds ratios of 3.90 (95% CI, 2.84 to 5.34) for the risk of schizophrenia in heavy cannabis users. 3 However, use of cannabis strains with high CBD content has been associated with fewer psychotic symptoms. 4 Whereas THC produces acute psychotic-like symptoms in healthy volunteers, pre-treatment with CBD decreases the THC-induced psychotic symptoms and cognitive impairments. 5-7

The potential beneficial effects of CBD on cognition in patients with schizophrenia have critical importance, since cognitive deficits are common in schizophrenia (up to 75%-85% of patients), usually precede other symptoms, and respond minimally to the available pharmacological treatments.

The very first case report on the use of CBD as an antipsychotic medication was published by Zuardi and colleagues 8 (Table). In this study, a 19-year-old female patient with schizophrenia was treated with CBD up to 1500 mg daily for 4 weeks, which resulted in improvement of acute psychotic symptoms. Findings from a study in 2006 that looked at the effects of CBD as monotherapy for treatment-resistant schizophrenia in three individuals show that improvement was seen in only one patient. 9 A later study on the antipsychotic effects of CBD (at flexible doses up to 400 mg/d) on 6 individuals who had Parkinson disease showed improvement of psychotic symptoms over the course of 4 weeks. 10

Since then, the antipsychotic properties of CBD have been investigated in three clinical trials with mixed results (Table). In 2012, Leweke and colleagues 11 published the first double blind randomized controlled clinical trial on the therapeutic effects of CBD (600-800 mg/d for 4 weeks) compared with amisulpride on acute psychosis in individuals with schizophrenia (N = 42). The study concluded that CBD is as effective as amisulpride in treating psychotic symptoms and has fewer adverse effects, including less extra pyramidal symptoms and weight gain.

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More recently, the effects of CBD on psychosis were explored in two double-blind randomized placebo-controlled clinical trials. McGuire and colleagues 12 used CBD as an adjunctive medication in treatment of acute psychosis in individuals who had schizophrenia or other non-affective psychotic disorders. Participants (N = 88) received either CBD 1000 mg daily (in two divided doses) or placebo in addition to their routine antipsychotic medications (continued unchanged during the study) for 6 weeks.

Compared with the placebo group, the CBD group showed greater improvement of positive psychotic symptoms over the course of the treatment. Mean improvement of PANSS positive score was 3.2 (SD 2.60) in the CBD group compared with 1.7 (SD 2.76) in the placebo group. Moreover, by the end of the treatment, more patients in the CBD group were rated as “improved” on the CGI-I scale compared with those in the placebo group (78.6% and 54.6%, respectively). Patients who received CBD also showed a trend-level improvement in their cognitive functioning, and a significant improvement of their motor speed compared with controls.

In a similar study, Boggs and colleagues 13 investigated the therapeutic effects of adjunctive CBD 600 mg daily (in two divided doses) compared with placebo in a 6-week double blind placebo-controlled randomized clinical trial, in individuals with chronic schizophrenia (N = 36). However, their results showed no significant differences between CBD and placebo on psychotic symptoms or cognitive performances.

Mechanism of action

The exact mechanism of action is still unknown for CBD’s potential anti-psychotic properties. Unlike other antipsychotic medications, CBD does not greatly affect dopaminergic neurons, and unlike THC, it does not bind to cannabinoid receptors. However, CBD reportedly increases the CSF levels of anandamide, one of the main endocannabinoid ligands, by blocking its degrading enzyme, fatty acid amide hydrolase, or by competing with anandamide intracellular transporters. It is interesting to note that anandamide levels are negatively correlated with severity of psychotic symptoms, whereas increased anandamide levels in psychotic patients treated with CBD are correlated with clinical improvement. This may suggest that CBD contributes to amelioration of psychosis by increasing the endogenous levels of anandamide. However, further studies are needed to confirm this.

The current pharmacological treatment for schizophrenia is only partially effective and mainly for positive symptoms. This has led investigators to investigate new pharmacological targets and the endocannabinoid system has been one of the newest ones. Over the past few decades, increasing evidence has shown the presence of endocannabinoid system abnormalities in schizophrenia. 14 However, the current studies on the potential therapeutic effects of CBD are not conclusive and the mechanism of action is poorly understood. The discrepancies in clinical results could be related to different doses of CBD, stages of psychosis, or possibly heterogeneity of schizophrenia itself.

Conclusion

In addition to the potential therapeutic effects of CBD for schizophrenia, CBD may also have a role in preventing or treating the psychosis related to recreational use of cannabis in vulnerable individuals. Cannabis continues to be the most commonly used illicit drug in the US, and with the spreading legalization for medical and recreational purposes, a lower proportion of people perceive the risk associated with regular cannabis use. At the same time, there is a decreasing ratio of CBD-to-THC in street cannabis from 1:14 in 1995 to 1:80 in 2014. Low CBD content may affect the overall impact of frequent cannabis use on mental health, which may become evident in the future. When discussing the medicinal use of cannabis, it is important to distinguish CBD, with its potential beneficial effects, from THC, with its controversial adverse effects, especially on individuals with psychotic disorders.

Disclosures:

Dr Bassir Nia is Assistant Professor of Psychiatry, Yale University School of Medicine, New Haven, CT. Dr Bassir Nia reports that she has no conflicts of interest concerning the subject matter of this article.

References:

1. US Food and Drug Administration. FDA Approves First Drug Comprised of an Active Ingredient Derived From M arijuana to Treat Rare, Severe Forms of Epilepsy. 2018. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm. Accessed February 7, 2019.

2. US Drug Enforcement Administration. FDA-Approved Drug Epidiolex Placed in Schedule V of Controlled Substance Act. 2018. https://www.dea.gov/press-releases/2018/09/27/fda-approved-drug-epidiolex-placed-schedule-v-controlled-substance-act. Accessed February 7, 2019.

5. Martin-Santos R, Crippa JA, Batalla A, et al. Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers. Curr Pharm Des. 2012;18:4966-4979.

6. Englund A, Morrison PD, Nottage J, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippoc ampal-dependent memory impairment. J Psychopharmacol. 2013;27:19-27.

7. Bhattacha ryya S, Morrison PD, Fusar-Poli P, et al. Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. 2010;35:764-774.

8. Zuardi AW, Morais SL, Guimaraes FS, Mechoulam R. Antipsychotic effect of cannabidiol. J Clin Psychiatry. 1995;56:485-486.

9. Zuardi AW, Hallak JE, Dursun SM, et al. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol. 2006;20:683-686.

10. Zuardi AW, Cripp JA, Hallak JE, et al. Cannabidiol for the treatment of psychosis in Parkinson disease. J Psychopharmacol. 2009;23:979-983.

14. Fakhoury M. Role of the endocannabinoid system in the pathophysiology of schizophrenia. Mol Neurobiol. 2017;54:768-778.