This post will explain the mechanisms why some people get psychosis symptoms from pot/marijuana. THC has been one of my favorite substances for food sensitivities and sleep quality, I know a lot of my clients don’t do well on THC so I wrote this post to explain the reasons why they get these negative reactions and some things they can do to mitigate them. You can also find many other substances I have tried to get rid of my food sensitivities and improve my sleep if you think THC is not for you in my ebooks, SelfHacked Secrets and Biohacking Insomnia.
There are a number of anecdotal reports that cannabis can produce a range of acute psychotic symptoms that include depersonalization, derealization, paranoia, flight of ideas, disorganized thinking, persecutory delusions, grandiose delusions, auditory and visual hallucinations, and impairments in attention and memory in an otherwise clear consciousness (R).
Studies show that in healthy volunteers, THC (from cannabis) can induce psychosis (R). However, some people experience more negative effects than others and in some cases result in long-lasting changes.
In recent years, there has been research linking cannabis use and schizophrenia-like psychotic disorders, and epidemiological evidence consistently suggest that the use of cannabis during adolescence increases the risk for psychotic disorders by 2-fold. However, no one knows for sure if cannabis causes schizophrenia.
Whether it causes schizophrenia or not, some people experience more negative psychotic effects (such as paranoia) and this post will address why this might be the case.
Cannabis Induced Psychosis and Neurotransmitters
THC increases dopamine in the striatum, which is a biological feature of schizophrenia and psychosis (R). Dopamine in the striatum is good in that it increases motivation and probably happiness, but if someone already has high dopamine in the striatum, cannabis can bring them over the edge.
CB1 receptor activation also increases dopamine in the Prefrontal Cortex, which might lead to non-specific activation and disrupt normal signal processing and result in poor cognitive integration of inputs. Too high levels of dopamine may contribute to working memory deficits associated with cannabis exposure (R).
Structural and functional imaging studies have shown that chronic cannabis causes the same negative changes in brain structure as schizophrenia, such as volume reduction in the hippocampus and the amygdala (R). This might be due to the neurotoxic effects of chronically elevated dopamine (R).
Activation of the CB1 receptor reduces GABA release in hippocampal neurons. This disrupts the synchronization of neuronal activity, which interferes with memory consolidation and brain’s ability to make normal associations, eventually leading to psychotic symptoms (R).
In other words, GABA puts the breaks on ‘crazy’ thoughts, and when CB1 receptors are activated, GABA is reduced in some key places(R).
Schizophrenics, likewise, have less GABA.
Cognitive gating functions in the brain prevent illogical or crazy thoughts from entering the conscious brain.
Several studies show that cannabinoids reduce glutamate (and NMDA activation) in several brain regions involved in the regulation of gating functions, such as the hippocampus, the prefrontal cortex, the nucleus accumbens, and the amygdala (R).
Ketamine, an NMDA blocker, also causes psychosis, demonstrating the role of lower glutamate in certain regions and psychosis.
Genes and Cannabis-Induced Psychosis
You can upload your genetic data to SelfDecode to see if you have these genes.
DRD2 (Dopamine Gene)
A large series of experimental data indicate that dopamine D2 receptors and schizophrenia are tightly related.
There is an association between psychosis and relatively greater D2 receptors in the striatum, a dopamine-rich area of the brain (R).
The DRD2 receptors are blocked of antipsychotic drugs and is their most important mechanism of action (R).
Relatively excessive dopamine D2 activation may lead to reduced ‘gating’ functions: reduced filtering of relevant information (reduced signal to noise ratio), as well as blocking out distractions (R, R).
Patients with schizophrenia performing attentional tasks have less activity and lower grey matter in the cingulate, a brain region that heavily influences attentional processing and executive function (R). This region is influenced by D2 receptors (R, R).
The “A” allele of rs1076560 in the Dopamine DRD2 gene is associated with Cannabis-induced psychosis (R).
It’s associated with a 10X higher risk of developing psychosis in daily cannabis users (R).
The A allele increased DRD2 function by making the DRD2 protein longer (decreases the ratio of D2S and D2L) (R)
The D2 long form (D2L) is mainly postsynaptic and is a target for antipsychotics (R). Mice without D2L receptors have reduced D2 activity (R). The D2 short (D2S) form is mainly a presynaptic autoreceptor that inhibits dopamine synthesis and release (R).
In healthy subjects, the interaction between the A allele of DRD2 rs1076560 and the A allele of AKT1 rs1130233 was associated with reduced AKT1 protein levels and increased GSK-3β, as well as with altered cingulate response and impaired cognitive function during attentional processing (R).
(Technical: AKT1 (and antipsychotics) phosphorylates GSK-3β at the Ser-9 residue, and inhibits its activity (R, R). Chronic anti-psychotics and lithium cause inhibitory phosphorylation of GSK-3β in the rat prefrontal cortex and striatum (R, R, R, R, R).)
COMT (Dopamine-Related Gene)
The COMT gene plays an important role in the degradation of dopamine in brain.
The “GG” variant of rs4680 is associated with increased COMT activity, which results in a combination of reduced dopamine in the prefrontal cortex and increased levels of dopamine in mesolimbic areas.
Individuals with “GG” display psychotic symptoms after use of cannabis during adolescence (R).
Another study reported that COMT genotypes only influenced development of psychotic disorders among individuals exposed to childhood abuse, indicating that environmental exposure and genetic factors may interact in a more complex way than expected (R) .
CB1 Receptor (Cannabinoid Gene)
Cannabinoid receptor type 1 (CB1) is the most well-characterized cannabinoid receptor. It seems that changes in this receptor can increase the risk of schizophrenia.
The cannabinoid system plays an important role in brain maturation during adolescence, which is a critical period for maturation of many neurotransmitters, including dopamine (R).
Some scientists suggest that abnormal CB1 function may hamper maturation of the neuronal networks during adolescence, which might underline the later development of psychosis (R).
In schizophrenia, it’s interesting that some studies have reported an increase in cannabinoid receptor (CB1) function in the dorsolateral prefrontal cortex and cingulate, which are associated with volume loss in these areas (R, R).
Counteracting The Psychotic Effects of Cannabis
It seems like inhibiting GSK3b is the best bet to counteracting cannabis-induced psychosis.
People with schizophrenia have less alpha 7 nicotinic receptors in their hippocampus, cortex and thalamus (R, R). In animal models, impaired auditory sensory gating has been linked to the alpha7 nicotinic receptor gene, and in turn, introducing alpha7 nicotinic agonists has been found to enhance auditory sensory gating (R, R).
One SNP (rs6494223) of this gene was associated with delusions in Alzheimer’s disease.
Alpha 7 nicotinic activators, such as nicotine and galantamine, may help counteract the working memory issues people face with schizophrenia (R).
Find out if any of these gene variations could be affecting your mental and physical health with SelfDecode. Your genes have a lot to tell you. Now you can finally start listening.
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