Antipsychotics change the effects of marijuana

CBD in the treatment of psychosis

Often warnings are given about the risk of psychosis when using cannabis, especially among young people. The risk of psychosis in cannabis users is said to be two to three times higher than that of non-users. However, the relationships are very complex and not yet fully understood, which is why this assumption cannot be confirmed with absolute certainty. Scientists now realize, however, that cannabis can presumably also protect against psychotic states.

Although the cannabinoid delta-9-tetrahydrocannabinol (THC) can promote the development of psychosis, the non-psychoactive cannabinoid cannabidiol (CBD) seems to have the opposite effect. This is not as absurd as it initially appears. Because in the brain there are numerous binding sites for cannabinoids and these are not only there to get a person "high", but because the body can produce them itself. These endocannabinoids are involved in the control of different processes. The phytocannabinoids from the cannabis plant THC and CBD intervene in these control circuits at different points with different effects. Recent studies suggest that CBD could be helpful in relieving symptoms of psychosis.

What is psychosis and how is it expressed?

Psychosis is a mental disorder in which perception and perception of reality can be significantly impaired. Since this mental disorder can show very different symptoms, there is no classic appearance by which it can be recognized.

However, there are some characteristics that are particularly common in those affected:

  • The loss of reality is characterized as a typical feature. The person concerned loses touch with what really is. He has perceptual disorders and can change significantly in his essence.
  • Those affected usually hear voices, feel persecuted and threatened by others. The threat can even come from people who are actually familiar and who are not recognizable as such to the person concerned. If an affected person hears voices, these can give him orders, threaten him or make him afraid.
  • In addition, the mental disorder can also lead to the person affected perceiving their body as being changed (body hallucinations).
  • Another noticeable feature that is often observed is the change in formal thinking. Affected people talk incoherently and confusedly, cannot concentrate and often change the subject for no reason.
  • In addition, they are listless and suffer from depressive moods, which lead to strong inner restlessness and can also have physical consequences such as temporary inability to move. As a result, psychotics can often no longer cope with their everyday lives without the help of others.

First signs

A variety of symptoms can occur in psychosis.

Since these symptoms do not appear in every psychotic and they can also occur in different forms, a psychotic may be difficult or impossible to identify as such. Even so, there are first signs that may indicate such a disease. Psychotics are withdrawing more and more from the outside world and giving up their social contacts. Depression, anxiety, and severe mood swings can also be the first signs.

So-called prodromal symptoms often occur, especially when the psychosis is not of organic origin. These are unspecific early symptoms such as social withdrawal, problems coping with everyday life, depression, anxiety, restlessness, listlessness, sleep and concentration disorders or the loss of joy in life.

Since these symptoms often appear months or even years before the actual onset of the disease, they are rarely associated with it. In addition, they can of course also be signs of other illnesses or can be traced back to psychological stress. As a result, non-organic psychoses are often recognized late and occur suddenly anyway.

Overview of common symptoms of psychosis

  • Hallucinations: Most psychotics hear commanding or commentary voices. It is also possible that she sees people, objects or flashes of light that are not there.
  • Thought disorders with regard to content: Those affected often feel persecuted or believe that they are receiving secret messages, for example through the radio. Megalomania is also a common symptom in which those affected are convinced that they are, for example, a superhero or a god. Obsessive-compulsive thoughts are also common symptoms.
  • Ego disorders: those affected perceive themselves as strangers. For example, they may think that their arm does not belong to them or they may think that they can read other people's minds. It is also possible that the person concerned believes that his thoughts are being stolen by an alien power (deprivation of thoughts).
  • Formal thought disorders: Often the vocabulary of the person concerned is limited and thinking is limited to a few topics (lack of thoughts). Thinking is often confused and important details can no longer be distinguished from unimportant ones. Some people affected have the feeling that the environment is not real (derealization) or one believes to be manipulated / controlled by an external force.

What are the causes?

The causes can be varied. A distinction is made between inorganic and organic causes:

Inorganic causes

A non-organic psychosis, on the other hand, has no physical cause and is therefore not organic. The development is therefore not fully traceable and it is difficult to clarify. In science, it is believed that an inorganic disorder is caused by the influence of various circumstances. Infections, trauma and environmental influences can influence the risk of non-organic psychosis, whereby individual susceptibility also plays a role. This is determined by genetics and makes some people particularly vulnerable to non-organic psychosis. Schizophrenia and affective disorders such as mania and depression are counted as non-organic disorders. The symptoms of both diseases can also occur in combination, one then speaks of a schizoaffective psychosis.

Organically determined causes

Organic disorder can be caused by organic disease, the use of psychostimulants, and side effects of a drug. Diseases such as tumors in the brain, epilepsy, Parkinson's or multiple sclerosis as well as trauma, postpartum depression or metabolic diseases can be the cause here. At the same time, this means that the underlying disease is treated with the therapy and can be completely regressed without having to be treated specifically.

Treatment and drug therapy

Medication compliance is often poor in patients with psychosis.

A psychosis should be recognized and treated as early as possible in order to promote therapeutic success. The therapy naturally also depends on whether the disease has an organic or non-organic cause and how severe it is.

In the case of a severe episode, an inpatient stay in a special specialist clinic is unavoidable. Mild episodes can usually be treated successfully on an outpatient basis or in a day clinic. This step is not always easy, because the sick are often not aware of their situation and refuse to cooperate. This is a difficult situation, especially for doctors and relatives, that demands strength and assertiveness.

If a non-organic disease is to be treated, the patient is usually given neuroleptics, which reduce the typical symptoms and have a positive effect on the patient's psychological state. Other drugs, such as antidepressants or lithium, can also be used.

What therapy options are there?

In addition, socio- or psychotherapies are carried out. These help to find out the causes and are intended to support those affected in being able to cope better with their everyday lives. Drug psychotherapy usually lasts for several years or is even permanent in order to avoid a relapse. It should be noted, however, that a non-organic disease can occur in different forms and can also be expressed as a single episode. So it doesn't have to be permanent. A patient can appear to be symptom-free between individual attacks.

The problem with many psychotics is that they repeatedly stop taking their medication on their own initiative because they consider themselves to be mentally healthy. As a result, those affected get a boost again. Carrying out permanent medication for a psychotic is usually impossible, which is why depot neuroleptics often have to be used.

If there is clearly an organic reason, another treatment is given. Because the main thing here is to remedy the cause. If a disease can be identified as the cause, it is important to treat it. That means, for example, removing a tumor or replacing drugs whose side effects triggered psychotic episodes.

If the underlying disease is successfully eliminated, it can be assumed that an organically caused psychosis will regress on its own. An acute physically caused psychosis usually has no lasting consequences and disappears completely. Psychotropic drugs can also be used while their cause is being treated to provide temporary help and alleviate symptoms.

Current studies on CBD and its antipsychotic effects

As early as 2012, researchers at the Ruhr University Bochum pointed out that there is a close relationship between cannabis, the endocannabinoid system and psychoses. A large number of animal and human studies have found dysregulation of endocannabinoid signaling pathways in psychosis. Elevated anandamide levels in schizophrenia patients, which correlate negatively with psychotic symptoms, indicate a protective role, while 2-arachidonoylglycerol counteracts psychosensitive cognitive impairments.

Thus, pharmacological manipulation of the endogenous cannabinoid system could be associated with potential antipsychotic properties. In the review article prepared by the researchers, it is said that the hypothesis of an antipsychotic effect of phytocannabinoids can be largely confirmed. Even with its pharmacological profile similar to that of atypical antipsychotics, cannabidiol appears to be superior.

In 2016, researchers at Heidelberg University saw the urgent need to develop new therapy options that have fewer side effects than standard antipsychotics. The endocannabinoid system was seen as a new potential target, while the chronic use of cannabis itself is seen as a risk factor for the development of psychosis, CBD does not seem to have this risk potential.

Although results from animal studies are to some extent contradicting and appear to be dependent on behavioral paradigms, treatment duration and experimental conditions, the non-psychoactive substance has shown antipsychotic properties in both rodents and rhesus monkeys.

After a few individual treatment attempts, the first randomized, double-blind, controlled clinical trial showed that the phytocannabinoid in acute schizophrenia has antipsychotic properties comparable to the antipsychotic amisulpride, while accompanied by a superior, placebo-like side effect profile.

Since the clinical improvement was significantly associated with increased anandamide levels, it seems likely that its antipsychotic effects are due to mechanisms associated with increased anandamide levels. Although a variety of mechanisms of action have been suggested, the potential relevance for which this effect remains remains to be investigated. The elucidation of these mechanisms as well as the establishment of the antipsychotic effectiveness of cannabidiol and the hopefully benign side effect profile are the subject of a number of clinical studies that have already started.

Antipsychotic Drugs, Dopamine Receptors, and the Effectiveness of CBD

CBD can reduce psychotic symptoms.

Even more interesting and up-to-date is a work by Prof. Philip McGuiere from Kings College in London. The researcher explains here that the antipsychotic effect can be explained by the fact that the active ingredients block the dopamine receptors. However, dopamine is not the only neurotransmitter (messenger substance) that is changed in its function in psychosis. In some people affected, dopamine function can also be normal, which is why a new therapy option that targets different neurotransmitter systems is necessary.

As part of the randomized study, 88 schizophrenia patients received either 1000 milligrams of CBD per day or a placebo in addition to the antipsychotic medication for six weeks. The psychotic complaints in the patients in the CBD group were significantly reduced.

Cannabidiol is a promising new drug due to a wide range of pharmacological effects.

To correlate the clinical effectiveness of CBD with its pharmacological mechanisms of action, the scientists conducted a bibliographic search of all clinical studies examining the use of CBD to treat psychiatric ailments.

The results so far suggest that cannabidiol

  • in schizophrenia can have an antipsychotic spectrum of activity mainly through endocannabinoid signaling and cannabinoid receptor type 1 antagonism
  • shows anxiolytic effects in patients with generalized social anxiety disorder through modification of cerebral blood flow in specific brain sites and serotonin 1A receptor agonism
  • Withdrawal symptoms reduced by modulating the endocannabinoid, serotoninergic and glutamatergic systems

The current evidence shows that the non-psychoactive phytocannabinoid has the ability to reduce psychotic, anxiety and withdrawal symptoms through various hypothetical pharmacological properties. However, further studies should include larger randomized controlled samples and examine the effects of CBD on biological measures to relate the clinical effects to possible changes in signal transduction by neurotransmitters and structural and functional cerebral changes.

New study at King’s College London

As part of their current study from 2018, the scientists analyzed a total of 33 test subjects in their early to mid-twenties who suffered from psychological symptoms and who were suspected of developing psychosis. The comparison was made with 19 healthy study participants (mean age of 23 years).

16 subjects who were suspected of having psychosis received a CBD dose of 600 milligrams. This dose had previously been shown to be effective in treating psychoses. In contrast, 17 study participants received a placebo.

Three hours later, all participants were examined in a magnetic resonance imaging scanner while performing a memory task with three regions of the brain. These areas of the brain are known to be involved in psychosis. The task was to show the participants word pairs. You then had to indicate whether these words could be linked to one another. Then later they had to remember these words.

Results of the investigation: CBD is shown to be effective against symptoms

Unsurprisingly, the brain activity of a suspected psychotic patient is abnormal compared to that of a healthy human. However, after a single dose of CBD, these patients' brain activity is less affected than that of those given a placebo.

The scientists believe their results could pave the way for a new treatment. Study author Dr. Sagnik Bhattacharyya stated in the result:

“The mainstay of current treatment for people with psychosis are antipsychotics, which weren't discovered until the 1950s and unfortunately don't work for everyone. We have started unraveling the brains of a new drug that works completely differently from traditional antipsychotics. "

Now the scientists are starting a large study to investigate whether CBD is suitable for treating people at risk of psychosis.

Cannabidiol is safe and well tolerated

Dr. Bhattacharyya continued: “One of the main advantages of cannabidiol is that it is safe and very well tolerated. That makes the substance an ideal drug in a way. If successful, this study will provide definitive evidence of cannabidiol's role as an antipsychotic agent and pave the way for clinical use. "

Conclusion

The interaction of the neurotransmitters (messenger substances) in the brain is very complex and not yet fully understood. If a neurotransmitter is influenced by drugs, this interaction can lead to disorders.These messenger substances, which presumably play a role in psychosis, also include the endocannabinoids (the body's own cannabinoids, which are similar to the cannabinoids from the cannabis plant).

In turn, the endocannabinoids are part of the endocannabinoid system in the body that attach to specific cannabinoid receptors and thus influence health. It has long been suggested that the endocannabinoid system and psychotic illness are related. Cannabidiol and tetrahydrocannabinol, like the endocannabinoids, can influence the endocannabinoid system.

The psychoactive cannabinoid THC is able to trigger psychotic symptoms in both healthy and psychotically ill people. Again, cannabidiol does not seem to promote the development of a psychotic illness, rather it can presumably suppress the symptoms. Much more research and clinical studies are needed here to better understand the exact mechanisms involved.

 

Note: In this article we report on prescription CBD or cannabidiol. This article makes no suggestion as to the possible purpose. Promises of use are left to the pharmacists.

 

Swell:

  • Department of Psychiatry, LWL University Hospital, Ruhr-University Bochum, Alexandrinenstr. 1-3, 44791 Bochum, Germany, Roser P1, house manager IS, 2012, "Antipsychotic-like effects of cannabidiol and rimonabant: systematic review of animal and human studies"