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. Schizophrenia is a neurological disorder affecting the perception of reality and cognition. We explore if CBD is safe and how it might help.
CBD Fights Schizophrenia, but with Different Dose Range for Different Symptoms
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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 Oil for Schizophrenia & Psychosis: Can It Help?
Schizophrenia is a neurological disorder affecting the perception of reality.
We explore if CBD is safe & how it might help.
Schizophrenia causes disordered thoughts and speech, visual or auditory hallucinations, and a myriad of other symptoms that can vary from one person to the next.
Researchers are continuously looking for new, effective treatment options for schizophrenia, and in recent years have turned their focus toward CBD — a powerful, medicinal (non-psychoactive) compound contained in the cannabis plant.
In this article, we’ll discuss what we know so far about this debilitating mental health condition and how CBD can be used to support symptoms.
MEDICALLY REVIEWED BY
Updated on November 13, 2021
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Can CBD Help With Schizophrenia?
Schizophrenia is a complex psychiatric disorder involving many different confounding factors working together to produce symptoms. Schizophrenia is a serious chronic, debilitating psychotic disorder listed in the top 15 leading causes of disability worldwide according to the National Institute of Mental Health.
This means that there is no single effective treatment for the disorder. Successful treatment, therefore, requires an all-encompassing approach. Everything from changes in diet and lifestyle to supplements and medications should be combined to manage the condition.
CBD has been shown to offer some unique benefits that may be combined with other treatments to maximize the management of schizophrenia.
While the mechanism of action for CBD remains unclear, the results so far have been promising.
The potential benefits of CBD oil for schizophrenia include:
- Alleviates anxiety & depression
- Regulates neurotransmitter balance (dopamine, serotonin, & glutamate)
- Increased blood flow to cortical regions of the brain
- Improves sleep quality & duration
- Regulates the vanilloid receptors (TRPV1)
What is Schizophrenia?
Schizophrenia is a diagnosable psychotic disorder involving delusions, hallucinations, disorganized speech, difficulty staying focused, lack of motivation, and disorganized or catatonic behavior. Diagnosis by a physician requires at least a month or two or more symptoms over at least six months, with at least one positive symptom and social/occupational dysfunction.
Seeing a doctor early is important because schizophrenia must be carefully distinguished from other mood and psychotic disorders with similar symptoms, in order to optimize correct treatment and minimize long-term harm.
However, it’s a rare condition affecting ~1% of the US population, according to the American Psychiatric Association. They also note that approximately half of schizophrenia patients may also suffer from another mental or behavioral disorder.
There are a lot of misconceptions in public understanding of this condition. Despite popular belief, most schizophrenics aren’t dangerous. They don’t all live in hospitals nor have split personalities. Many, albeit not most people, who have the condition can live reasonably normal lives — they often have jobs and families and can live independently.
Schizophrenia affects both men and women equally, but symptoms tend to appear sooner in males than females. Men usually begin experiencing symptoms around their late-teens to mid 20s, while females typically start showing signs in their mid 20s or early 30s. It’s rarer for anybody under the age of 12, or over 40, to show symptoms of schizophrenia — but still possible.
Schizophrenia itself isn’t deadly, but it’s often associated with other medical conditions that can lead to problems later in life — such as heart disease or diabetes. Patients, in general, are at higher risk of premature death from such preventable causes, also including metabolic and liver disease, and suicide.
Three Phases of Schizophrenia
1. Prodromal Phase
This is the phase leading up to the first display of active psychotic symptoms, usually starting here with negative symptoms. “Negative” symptoms can be thought of as irregular social behaviors or speech/affect opposite of the norm (listed below). There is also some accompanying decline in daily functioning. If detected early enough, the onset and severity of schizophrenia can be significantly reduced and better managed in the long-term .
In the prodromal phase, patients often experience a decline in social and cognitive functions like memory, judgement, attention, depression, anxiety, isolation, and learning difficulties. Patients may also have mood symptoms such as depression, anxiety, and suicidal thoughts which should be taken seriously.
The prodromal phase can last anywhere from several weeks to several years .
2. Active Phase
During this phase, distinct positive symptoms become evident and perhaps more severe, involving delusions, hallucinations, and catatonic behavior. These “positive” symptoms may involve delusions, hallucinations, disorders of thought, and either agitation/aggression or catatonic behavior. This is when treatment is most important and when most schizophrenia diagnoses are made.
3. Residual Phase
In the residual phase, symptoms may begin to disappear, but patients are often left feeling “flat,” with poor motivation, low mood, and inability to focus or concentrate. Treatment during this phase is still important, directed toward controlling psychotic episodes and mood symptoms.
In the long run, about 30% will improve or return to normal function, another 30% will be hospitalized intermittently, and another 30% will be institutionalized or incapacitated. Unfortunately, ~10% of patients are lost to suicide.
Signs & Symptoms of Schizophrenia
The symptoms of schizophrenia can be divided into three main categories:
A) Positive (Psychotic) Symptoms
B) Negative Symptoms
C) Cognitive Symptoms
What Causes of Schizophrenia?
Unfortunately, there isn’t a single identified cause of schizophrenia. Research has linked the disorder with some different potential causes, including environmental influences, genetics (i.e. chromosome 6), changes in brain chemistry, and physical or emotional trauma.
1. Dopamine Theory
One of the leading theories for the causes of schizophrenia comes from early behavioral studies that found if you increase dopaminergic activity in certain brain pathways then psychotic symptoms appear (as in overdoses of cocaine, amphetamine, L-dopa).
This mesocorticolimbic projection is now the primary target mechanism of antipsychotic drugs.
In fact, all anti-psychotic medications work by blocking dopamine (D2) receptors in the brain to some degree — suggesting that schizophrenia is caused by too much dopamine in certain brain pathways.
The trade-off is that either over-activating or blocking dopamine in certain brain areas may cause unpleasant side-effects, which can be addressed.
For example, blocking dopamine receptors in one area produces Parkinsonian-like effects and involuntary muscle spasms. Too little dopamine activity in the frontal cortex is thought to cause the negative and cognitive symptoms.
First generation anti-psychotics are effective at blocking psychotic symptoms, however, they often come with many other side effects. Second generation (or “atypical”) anti-psychotics are better at avoiding the side-effect pathways, and also block a greater number of serotonin receptors.
2. Brain Structure Abnormality Theory
Neuroimaging studies have shown that patients with differing symptoms have physiological abnormalities (such as reduced blood flow) in different areas of the brain.
For example, patientshave been shown to have abnormalities in the thalamus — the area of the brain tasked with filtering and processing sensory signals such as sight, sound, or touch. Other studies have found that patients show signs of reduced neurons, which may be related to the faulty, overactive C4 pruning gene researchers found on chromosome 6.
All of these different factors suggest that schizophrenia can be caused by dysfunctions in many different areas of the brain. Symptoms will be determined by the parts of the brain that are most affected.
Low doses of cannabis improve blood flow to regions of the brain involved with regulating mood, sociability, and cognition — potentially reducing psychotic symptoms associated with schizophrenia .
3. Glutamate Theory
Glutamate is the most abundant neurotransmitter in the brain, and the one responsible for neural excitement. One theory regarding schizophrenia involves inappropriate glutamate activity and NMDA receptor expression alteration in the brain. This theory could be used to explain many of the symptoms associated with the condition. Additionally, the psychoactive drug phencyclidine (PCP) is known for producing acute, schizophrenia-like psychosis through activation of the glutamate receptors in the brain .
This has led some medical researchers to suggest schizophrenia involves similar over- or underactivation of glutamate in certain areas of the brain.
Studies show that synthetic cannabinoids reduce PCP-induced schizophrenic symptoms in rats .
4. Anandamide Excess Theory
Other research findings suggest schizophrenic patients have significantly higher levels of anandamide in their blood . Follow up studies show high levels of anandamide present in the cerebrospinal fluid of actively psychotic, schizophrenic patients who have never been treated. Interestingly, researchers now pose that high anandamide may not be the cause, but is actually a homeostatic compensation to fight the disease state.
In a double-blind, randomized clinical trial, CBD was shown to improve psychotic symptoms by improving anandamide signalling. CBD was just as effective as the potent, second generation antipsychotic amisulpride at reducing symptoms — but had less unpleasant side effects.
CBD inhibits the enzyme FAAH from degrading anandamide, suggesting the endocannabinoid system is somehow altered in schizophrenia, but may now play a new role in treatment.
Similar studies report dysfunctional CB1 receptor activity in schizophrenic patients, especially in regions of the brain relating to cognition and memory — two functions highly compromised in schizophrenia [5, 6].
Patients with schizophrenia are more likely to be negatively affected by THC — which is a well-known CB1 receptor agonist .
This, of course, makes schizophrenia challenging to treat because there are so many different factors to take into account. It also explains why some patients respond to treatment, and others don’t.
5. Other Potential Causes
- Severe or long-term stress
- Substance abuse, particularly in adolescence
- Genetic factors
- Viral infection
- Developmental problems
- Autoimmune disorders
- Neurodegenerative disorders
Treatment Options for Schizophrenia
The most effective treatments for schizophrenia have an all-encompassing approach. Medications, lifestyle coaching, psychiatric care, and group therapy are all necessary aspects of treatment for this condition.
With early and proper treatment involving antipsychotic medications, most of the symptoms of schizophrenia can be reduced or eliminated, and episodes of active-phase schizophrenia become less frequent.
Unfortunately, all of these medications come with potentially negative side-effects, especially in the long term. Sudden, abnormal or painful muscle movements, diabetes, and heart complications are especially common in people taking these medications. There’s also a risk of CBD interacting with medications, so always talk to your doctor first.
However, side effects can be addressed with your doctor and managed if they appear. Families should seek support for their affected loved ones and themselves, with assistance like home care and ensuring patients can access and maintain treatment long-term.
Communities should provide opportunities for employment and assisted/independent living, giving patients a base from which to set and achieve goals.
Treatment for Schizophrenia May Include:
Medications Often Used For Schizophrenia:
What the Research Says: CBD Oil for Schizophrenia
Over the past decade, there’s been a growing interest in the use of CBD for treating schizophrenia.
This research started following a case report released in 1995 highlighting the improvement in a schizophrenic patient who was unresponsive to the standard antipsychotic medication haloperidol . In 2012, the results of the clinical study highlighted above on CBD vs amulisopride and enhanced anandamide signalling was published.
Even more recently, the pharmaceutical company GW Pharmaceuticals Plc recently ran a series of clinical trials on a new CBD-based drug it’s been developing called Sativex®. One of these studies explored whether or not CBD was able to relieve symptoms of schizophrenia in patients who were unresponsive to standard antipsychotic medications .
The GW Pharmaceuticals study was a phase 2, double-blind clinical trial conducted across 15 different hospitals in the UK, Romania, and Poland. Patients in the study were randomly put into either a treatment group (using 1000 mg per day of CBD split into two doses) or a control group (using a placebo).
At the end of the six-week trial, the CBD group showed modest improvements in schizophrenic symptoms. The most substantial improvements from the study involved motor speed and executive functioning.
The most significant finding in this research was that CBD didn’t appear to rely on dopamine receptor modulation — which is the primary target for current schizophrenia treatments. Instead, researchers in this study suggested the mechanism of action to be through inhibition of fatty acid amide hydrolase (FAAH), inhibition of adenosine reuptake, vanilloid receptor activation (VR1), and serotonin (5HT1A) receptor activation .
They concluded by stating that: “Because CBD acts in a way different from conventional antipsychotic medication, it may represent a new class of treatment for schizophrenia.”
More clinical trials are scheduled to explore the use of CBD for schizophrenia in larger populations and longer duration of treatment.
Results of the GW Pharmaceuticals Research Study:
(Source: McGuire et al., 2017)
THC vs. CBD for Schizophrenia
High-THC and low-CBD extracts have been associated with a higher risk of psychotic episodes . Other studies have shown that cannabis containing a high level of CBD and a level of low THC is associated with a lower risk of psychotic episodes .
Other studies have shown that CBD offered improvement in symptoms of schizophrenia to a similar degree as amisulpride — an antipsychotic medication . CBD also had fewer side-effects.
The differences between CBD and THC and their effect on schizophrenia is very important — and likely to be the reason behind the conflicting evidence for cannabis users and schizophrenia. Some patients find relief from symptoms with cannabis use; others experience dramatically worsened symptoms after using cannabis.
It is not recommended, but if using cannabis for schizophrenia, make sure you pay attention to the THC content. Additionally, only choose products with low or “not detectable” THC concentrations when buying CBD.
Key Takeaways: Using CBD for Schizophrenia
Schizophrenia is a highly complex neurological disorder that continues to puzzle medical researchers. However, there are several significant theories about the underlying causes of schizophrenia.
Some patients respond very well to medications; others do not.
Although CBD may improve the side-effects of the condition using several different models of schizophrenia (clinical and PCP-induced), there is also evidence that other cannabinoids — namely THC — can worsen schizophrenia.
For this reason, it’s recommended that you only use CBD for schizophrenia under the close watch of a medical professional. It’s also recommended that you only use CBD products that are entirely void of THC. Additionally, research suggests that a high dose (1000 mg per day) of CBD is needed to produce even modest improvements in symptoms.
Patients and families are encouraged to seek further support and resources from their doctor, and groups like NAMI and the American Psychiatric Association.