Further research into cannabinoid treatment as adjunct


Schizophrenia is a complex mental disorder that makes it difficult to:

  • Tell the difference between real and unreal experiences
  • Think logically
  • Have normal emotional responses,
  • Behave normally in social situations

Causes, incidence, and risk factors

Schizophrenia is a complex illness.  Mental health experts are not sure what causes it.  However, genetic factors appear to play a role.

  • Certain environmental events may trigger schizophrenia in people who are genetically at risk for it.
  • You are more likely to develop schizophrenia if you have a family member with the disease.

Schizophrenia affects both men and women equally.  It usually begins in the teen years or young adulthood, but may begin later in life.  It tends to begin later in women, and is milder.

Childhood-onset schizophrenia begins after age five.  Childhood schizophrenia is rare and can be difficult to tell apart from other developmental disorders of childhood (like autism).


Schizophrenia symptoms usually develop slowly over months or years.  Sometimes you may have many symptoms, and at other times, you may only have a few.

People with any type of schizophrenia may have difficulty keeping friends and working.  They may also have problems with anxiety, depression, and suicidal thoughts or behaviors.

At first, you may have the following symptoms:

  • Irritable or tense feeling
  • Difficulty sleeping
  • Difficulty concentrating

As the illness continues, problems with thinking, emotions and behavior develop, including:

  • Lack of emotion (flat affect)
  • Strongly held beliefs that are not based in reality (delusions)
  • Hearing or seeing things that are not there (hallucinations)
  • Problems paying attention
  • Thoughts "jump" between unrelated topics (loose associations)
  • Bizarre behaviors
  • Social isolation

Symptoms can vary, depending on the type of schizophrenia you have

Paranoid schizophrenia symptoms may include:

  • Anxious
  • Angry or argumentative
  • False believes that others are trying to harm you or your loved ones.
    Disorganized schizophrenia symptoms may include:
  • Problems with thinking and expressing ideas clearly
  • Childlike behavior
  • Showing little emotion

Catatonic schizophrenia symptoms may include:

  • Lack of activity
  • Muscles and posture may be rigid
  • Grimaces or other odd expressions on the face
  • Does not respond much to other people Undifferentiated schizophrenia symptoms may include symptoms of more than one other type of schizophrenia. People with residual schizophrenia have some symptoms, but not as many as those who are in a full-blown episode of schizophrenia.

Signs and tests

There are no medical tests to diagnose schizophrenia.  A psychiatrist should examine the patient to make the diagnosis.  The diagnosis is made based on a thorough interview of the person and family members.  The doctor will ask questions about:

  • How long the symptoms have lasted
  • How the person's ability to function has changed
  • Developmental background
  • Genetic and family history
  • How well medications have worked

Brain scans (such as CT or MRI) and blood tests may help to rule out other disorders that have similar symptoms to schizophrenia.


During an episode of schizophrenia, you may need to stay in the hospital for safety reasons.


Antipsychotic medications are the most effective treatment for schizophrenia.  They change the balance of chemicals in the brain and can help control symptoms.

These medications are usually helpful, but they can cause side effects.  Many of these side effects can be improved, and should not prevent people from seeking treatment for this serious condition.

Common side effects from antipsychotics may include:

  • Sleepiness (sedation)
  • Dizziness
  • Weight gain
  • Increased chance of diabetes and high cholesterol
  • Feelings of restlessness or "jitters"
  • Slowed movements
  • Tremor

Long-term use of antipsychotic medications may increase your risk for a movement disorder called tardive dyskinesia.  This condition causes repeated movements that you cannot control, especially around the mouth.  Call your doctor immediately if you think you may have this condition.

When schizophrenia does not improve with several antipsychotics, the medication clozapine can be helpful.  Clozapine is the most effective medication for reducing schizophrenia symptoms, but it also tends to cause more side effects than other antipsychotics.
Schizophrenia is a life-long illness.  Most people with this condition need to stay on antipsychotic medication for life.


Supportive therapy may be helpful for many people with schizophrenia.  Behavioral techniques, such as social skills training, can be used to improve social and work functioning.  Job training and relationship building classes are important.

Family members of a person with schizophrenia should be educated about the disease and offered support.  Programs that emphasize outreach and community support services can help people who lack family and social support.

Family members and caregivers are often encouraged to help people with schizophrenia stick to their treatment.

It is important that the person with schizophrenia learn how to:

  • Take medications correctly and how to manage side effects
  • Notice the early signs of a relapse and what to do if symptoms return
  • Cope with symptoms that occur even while taking medication.  A therapist can help.
  • Manage money
  • Use public transportation

Expectations (prognosis)

The outlook for a person with schizophrenia is difficult to predict.  Most of the time, symptoms improve with medication.  However, others may have difficulty functioning and are at risk for repeated episodes, especially during the early stages of the illness.

People with schizophrenia may need supported housing, job training, and other community support programs.  People with the most severe forms of this disorder may not be able to live alone.  Group homes or other long-term, structured places to live may be needed.

Symptoms will return if a person with schizophrenia does not take their medication.


Having schizophrenia increases your risk of,

  • Developing a problem with alcohol or drugs:  this is called a substance abuse problem.  Using alcohol or other drugs increases the chances your symptoms will return.
  • Physical illness:  People with schizophrenia may become physically sick, because of an inactive lifestyle and side effects from medication.  A physical illness may not be detected because of poor access to medical care and difficulties talking to health care providers.
  • Suicide


There is no known way to prevent schizophrenia.
Symptoms can be prevented by taking medication.  You should take your medication exactly as your doctor told you to. Symptoms will return if you stop taking your medication.
Always talk to your doctor if you are thinking about changing or stopping your medications.  See your doctor or therapist regularly.

Calling your health care provider

Call your health care provider if:

  • Voices are telling you to hurt yourself or others.
  • You feel the urge to hurt yourself or others.
  • You are feeling hopeless or overwhelmed.
  • You are seeing things that are not there.
  • You feel you cannot leave the house.
  • You are unable to care for yourself.

Schizophrenia and Cannabis

It has been found that Cannabidiol may have a calming, stabilizing effect on the brain - which may help to counteract some of the damage in the brain caused by THC.
Researchers hope to formulate a new medication for schizophrenia based on Cannabidiol.
According to a study that compared this active ingredient, Cannabidiol, with a leading antipsychotic drug (Amisulpride), Cannabidiol might inhibit psychotic symptoms in people with schizophrenia, causing fewer side effects.
Lead researcher of the study, Dr Marcus Leweke, of the University of Cologne, noted:
"There is a possibility that there are good guys and bad guys in cannabis.  THC is the bad person, but there is a small body of literature that suggested CBD might prevent the induction of psychotic symptoms.  Our study supports that view.  A systematic literature review has suggested the intriguing possibility that habitual

Cannabis use may protect cognitive function in schizophrenia patients, and CBD has been shown to improve a marker of this in healthy subjects.  There are preliminary data to suggest that:
Cannabinoids may have beneficial effects on abnormal stress reaction, metabolic dysfunction and dyslipidaemia.  Since the mechanism of action for the anti-psychotic effects of CBD and other cannabinoids almost certainly differs from all existing agents, synergistic combinations with both typical and atypical antipsychotics are a possibility. 
Taken overall, these observations lead to the hypothesis that an appropriately formulated medicine containing a combination of selected cannabinoids may have the potential to target all the major components of the schizophrenia syndrome and thereby significantly reduce the need for polypharmacy.

EVIDENCE suggests that cannabinoid receptors, the pharmacological target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia  Elevated anandamide and palmitylethanolamide levels in cerebrospinal fluid of schizophrenic patients may reflect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia.

Disturbances in the endogenous cannabinoid (ECB) system in schizophrenia may contribute to their enhanced sensitivity to psychoactive substances, and the beneficial effects of second-generation antipsychotics for substance abuse in schizophrenia may involve modulator effects on ECB.  Disturbances in the endogenous cannabinoid (ECB) system in schizophrenia may contribute to their enhanced sensitivity to psychoactive substances; baseline anandamide levels were significantly higher in patients, relative to controls.  This result is consistent with studies describing ECB dysfunctions in schizophrenia.  Improvements in substance abuse were probably not mediated by modulator effects.  Anandamide is a potential target for medications aimed at relieving SUD in schizophrenia.

Evidence suggests that cannabinoid receptors, the pharmacological target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia.  To test this hypothesis, we examined whether endogenous cannabinoid concentrations in cerebrospinal fluid of schizophrenic patients are altered compared to nonschizophrenic controls.  Endogenous cannabinoids were purified from cerebrospinal fluid of 10 patients with schizophrenia and 11 non-schizophrenic controls by high-performance liquid chromatography, and quantified by isotope dilution gas-chromatography/mass-spectrometry.  Cerebrospinal concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were significantly higher in schizophrenic patients than non-schizophrenic controls.  By contrast, levels of 2-arachidonylglycerol, another endogenous cannabinoid lipid, were below detection in both groups.  The findings did not seem attributable to gender, age or medication.  Elevated anandamide and palmitylethanolamide levels in cerebrospinal fluid of schizophrenic patients may reflect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia.

Cannabinoids for the Treatment of Schizophrenia?  A Balanced Neurochemical Framework for both Adverse and Therapeutic Effects of Cannabis Use

Clinic of Psychiatry, Social psychiatry & Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany, mueller-vahl.kirsten@mh-hannover.de

Highlighting the association between schizophrenia and cannabis sativa and the endogenous cannabinoid receptor system, respectively, two opposite aspects are of major relevance.  On the one hand, there is substantial evidence that cannabis has to be classified as an independent risk factor for psychosis that may lead to a worse outcome of the disease.  This risk seems to be increased in genetically predisposed people and may depend on the amount of cannabis used.  On the other hand, there are several lines of evidence suggesting that, at least in a subgroup of patients, alterations in the endocannabinoid system may contribute to the pathogenesis of schizophrenia, e.g., increased density of cannabinoid receptor type 1 (CB1) binding and increased levels of cerebrospinal fluid (CSF) anandamide.  Accordingly, beside the dopamine hypothesis of schizophrenia a cannabinoid hypothesis has been suggested.  Interestingly, there is a complex interaction between the dopaminergic and the cannabinoid receptor system.  Thus, agents that interact with the cannabinoid receptor system such as the non-psychoactive cannabidiol (CBD) have been suggested for the treatment of psychosis.

Cannabinoid Hypothesis of Schizophrenia: Cognitive Impairments Due to Dysregulation of the Endogenous Cannabinoid System

Cognitive impairments during psychotic episodes are assumed to be caused not only by one single putative classical neurotransmitter dysfunction but also by an impaired equilibrium of the interaction between different neurobiological generators of cognitive processes.  Herein, the perceptual abnormalities induced by psychogenic agents play a major role as tools for the understanding of model psychoses.  The recently discovered cannabinoid receptor system with its endogenous ligand anandamide can be regarded as an extremely relevant regulator system, a dysfunctionality of which may explain at least one subtype of endogenous psychoses.
Background: - The CB1 receptor is a protein in the brain that is targeted by the active ingredients in cannabis (marijuana).  Brain systems that react to cannabis may be involved in the causes and symptoms of schizophrenia and schizoaffective disorder.  For instance, research studies have shown that the number of CB1 receptors may be different in people with schizophrenia, and there may be differences in the receptors themselves.  Researchers are interested in using positron emission tomography (PET) to study CB1 receptors in people with and without schizophrenia, using a chemical tracer that attaches specifically to CB1 receptors.


relating to the association between cannabis and psychosis may be divided into two groups.  The exogenous hypothesis, which has received far greater attention, suggests that the consumption of cannabinoid compounds produces psychotic disorders by mechanisms that are extrinsic to the pathophysiology of naturally occurring psychoses.  Converging evidence from epidemiological, genetic, neurochemical, pharmacological and postmortem studies have provided support for an association between ‘cannabis and madness’.  These data also suggest a second, endogenous hypothesis, according to which cannabinoid (CB1) receptor dysfunction may contribute to the pathophysiology of psychosis and/or schizophrenia, and further, that the putative CB1 receptor dysfunction may be unrelated to the consumption of cannabinoid compounds.

The exogenous hypothesis of cannabis consumption and psychosis.

  Tetrahydrocannabinol (Δ9-THC) in patients with schizophrenia and normal controls.  A potential endocannabinoid contribution to the pathophysiology of schizophrenia.

The brain endocannabinoid (EC) system is a recently discovered brain neurotransmission system, which involves endogenous cannabinoid agents (ECs) that act upon specific receptors (CB1 and CB2).  CB1 receptor is abundant in the human brain and acts as an inhibitory modulator of classical neurotransmitters.  ECs and CB1 receptors appear to be involved in the pathophysiology of schizophrenia.  EC levels are elevated in the cerebrospinal fluid of patients with schizophrenia, and post-mortem studies have shown increased density of radioligand binding to brain CB1 receptors.  To what extent CB1 receptors are involved in, the pathophysiology of schizophrenia in the living human brain is currently unknown.  The lack of suitable methods to reliably quantify CB1 receptors in the living human brain, have to date hindered the progress in this field.
The aim of this project is to explore CB1 receptor abnormalities in human patients with schizophrenia.  The primary hypothesis is that CB1 receptor density is increased in patients with schizophrenia in comparison with healthy subjects.  Insight into the role of CB1 receptor function in schizophrenia may help guide future development of pharmacy co-therapies.

The CB1 receptors in schizophrenia patients suggest a potential relationship between behavioral characteristics and CB1 binding and provide clues to CB1 involvement in schizophrenia.


It is possible that subjects with schizophrenia that have an inherent tendency to a particular symptomatology have abnormal VT values.  It maybe even possible that VT values may help predict those that are at greater  risk of early decline into the negative syndrome of schizophrenia.

Elevated endogenous cannabinoids in schizophrenia.

Cannabis use is common amongst people with schizophrenia and regular use, even at relatively low levels, can have a negative impact on illness course (Hall and Degenhardt, 2000).  The effective management of this clinical problem is increasingly the focus of psychiatric practice and research...  Rather than attempt to explain fully the complex relationship between cannabis and psychosis, (negative impact that cannabis use may be having on their mental state).  Understanding the motivation for cannabis use may provide insight into this problem.
However, evidence exists for a subgroup of the population to suggest that cannabinoids have therapeutic effects on the negative and positive symptoms, as well as cognitive impairments.  The potentially therapeutic effects of cannabinoids.  Whilst the neurochemical effects of cannabinoids are complex, cannabinoids appear to have at least in part, a “restorative” effect on neurotransmitter dysfunctions in schizophrenia, which may underpin the biological substrate of the therapeutic effects cannabis has been demonstrated to have in recent studies.

In the context of recent research by ( Coulston et al.),  future studies need to establish which subgroups of schizophrenia most benefit from cannabinoids as a putative “treatment”;  which subgroups demonstrate nil or minimal exacerbation of positive symptoms in the context of cannabis use, or indeed, which subgroups may experience antipsychotic effects of cannabis;  how such a treatment may complement or interact with standard antipsychotics and other psychiatric treatments;  what constitutes an effective quantity or dose of cannabinoids to exert a beneficial impact on cognition;  what precise frequency of administration would be required; how long the effects of cannabinoids last on cognition following a recent dose;  how such a treatment may generalize to other domains of real-life functioning such as employment and social settings (and in particular, cognitive processes required to function well in these settings); and whether such a treatment can be generalized to older age groups.  Methods by which future research could proceed to address these questions include randomized, double blind, and controlled drug trials.

There are various factors to be considered in understanding why people with psychotic disorders continue to use cannabis.  These include: (1) level of insight into both their mental illness and the effects of cannabis on symptoms; (2) biological drives for cannabis use (e.g. dopaminergic); (3) genetic or learned family influences; (4) sociocultural influences; (5) impact of affective/psychotic symptoms; (6) personality variables and coping strategies; and (7) addiction.  It is argued, however, that the final common pathway or motivation to use cannabis is (8) the expectations of the direct and indirect effects cannabis use will have on affect.

In contrast, considerable interest in the potential role of the non-psychoactive, naturally occurring cannabinoids like:  {(cannabidiol (CBD)} as an anti-psychotic medicine also needs to be developed.


It seems to me that medical marijuana with low THC levels and high CBD levels could be used successfully as an adjunct in the treatment of Schizophrenia.  One of the main reasons I say this is because cannabis has so few side effects, so unlike pharmaceuticals.

Best:  Indica dominant hybrid with higher CBD levels.
Used as a tincture (oil or glycerin) based.  (Not alcohol)


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