Psychedelics Have Potential to be Physically Addictive

[HeavenlyBlue]

Hallucinogens act on serotonin 5-HT2a and 5-HT2c receptors as complete or partial agonists. They also form linked hetero-complexes with dopamine D2 receptors.

Dopamine D2 and 5-hydroxytryptamine 5-HT(₂A) receptors assemble into functionally interacting heteromers - PubMed), Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors - PubMed


This link has been postulated to account for the anti-psychotic effect of 5-HT2a antagonists in the treatment of schizophrenia. Dopamine antagonists have been used to treat this disease.

Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action - PubMed

The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotic drugs modulate information processing in cortico-limbic circuits via dopamine D2 receptor blockade in nucleus accumbens (NAc) whereas atypical antipsychotic drugs preferentially...

www.ncbi.nlm.nih.gov

5-HT2a agonism has been demonstrated to cause an efflux of dopamine in the cerebral cortex.

5-HT(2A) and 5-HT(2C) receptor stimulation are differentially involved in the cortical dopamine efflux-Studied in 5-HT(2A) and 5-HT(2C) genetic mutant mice - PubMed

Both 5-HT(2A) and 5-HT(2C) receptors modulate cortical dopamine efflux, but in opposite directions. We have now compared the ability of the three 5-HT(2A/2C) receptor agonists, DOI (R(-)-2,5-dimethoxy-4-iodoamphetamine), mCPP (meta-chlorophenylpiperazine) and MK-212 (6-Chloro-2-(piperazinyl)...

www.ncbi.nlm.nih.gov

5-HT2a receptors are localized in the nucleus accumbens, an area of the brain that is central to mechanisms involved with reward and addiction.

Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action - PubMed

The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotic drugs modulate information processing in cortico-limbic circuits via dopamine D2 receptor blockade in nucleus accumbens (NAc) whereas atypical antipsychotic drugs preferentially...

www.ncbi.nlm.nih.gov

5-HT2a receptor agonism enhances dopamine receptor (D2R) signaling.

Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes - PubMed

When 5-HT2a receptor density is elevated, the behavioral effects of cocaine become more pronounced.

Elevated Expression of Serotonin 5-HT(2A) Receptors in the Rat Ventral Tegmental Area Enhances Vulnerability to the Behavioral Effects of Cocaine - PubMed

The dopamine mesocorticoaccumbens pathway which originates in the ventral tegmental area (VTA) and projects to the nucleus accumbens and prefrontal cortex is a circuit important in mediating the actions of psychostimulants. The function of this circuit is modulated by the actions of serotonin...

www.ncbi.nlm.nih.gov

5-HT2a receptors are also involved in cue-induced reinstatement of MDMA-seeking behaviour. Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviour - PubMed



While withdrawal symptoms don't occur after using psychedelics, this does not mean that they do not alter reward seeking behavior. You may find yourself obsessed with integrating your experience. You may feel an afterglow, probably due to the upregulated activity of D2R following the use of psychedelics. You may find that the drug and the drug-induced state occupy your thoughts, so much that you spend many hours discussing and philosophizing about what it all means. Meanwhile, the plant from which it came is cultivated. You grow only the ones with the highest concentration of goodies. You do this for 100,000 years. You find that the drug induced state changes your behavior, even when it wears off. You feel a sense of interconectedness. You have a love for others that wasn't there before. This you attribute not to the drug, but to your voluntary thoughts. Your voluntary thoughts changed your behavior. Right?

 

[iorrus]

Are you being serious or just joking?

 

[Ufostrahlen]

Goodman & Gilman’s The Pharmacological Basis of THERAPEUTICS twelfth edition

24. Drug Addiction
Charles P. O’Brien

Tolerance, Physical Dependence, and Withdrawal. Frequent, repeated use of psychedelic drugs is unusual, and thus tolerance is not commonly seen. Tolerance does develop to the behavioral effects of LSD after three or four daily doses, but no withdrawal syndrome has been observed. Cross-tolerance among LSD, mescaline, and psilocybin has been demonstrated in animal models.

Pharmacological Intervention. Because of the unpredictability of psychedelic drug effects, any use carries some risk. Dependence and addiction do not occur, but users may require medical attention because of “bad trips.”

 

[HeavenlyBlue]

Goodman & Gilman’s The Pharmacological Basis of THERAPEUTICS twelfth edition

24. Drug Addiction
Charles P. O’Brien

Tolerance, Physical Dependence, and Withdrawal. Frequent, repeated use of psychedelic drugs is unusual, and thus tolerance is not commonly seen. Tolerance does develop to the behavioral effects of LSD after three or four daily doses, but no withdrawal syndrome has been observed. Cross-tolerance among LSD, mescaline, and psilocybin has been demonstrated in animal models.

Pharmacological Intervention. Because of the unpredictability of psychedelic drug effects, any use carries some risk. Dependence and addiction do not occur, but users may require medical attention because of “bad trips.”

DMT tolerance goes away within an hour.

If frequent and repeated use is uncommon, why does this forum exist?

 

[Ufostrahlen]

Why does this forum exist?

Because the forum is highly addictive and causes dependence very quickly.

 

[dmt_spider]

DMT tolerance goes away within an hour.

If frequent and repeated use is uncommon, why does this forum exist?

So does that mean motorbikes are addictive as there are hundreds of popular forums for them? Or weightlifting? Or knitting?

 

[HeavenlyBlue]

DMT tolerance goes away within an hour.

If frequent and repeated use is uncommon, why does this forum exist?

So does that mean motorbikes are addictive as there are hundreds of popular forums for them? Or weightlifting? Or knitting?

Weightlifting gets you really high. Just ask Arnold. He says it's better than sex.

Motorcycles get your adrenaline fix like no other.


I have also found scientific literature supporting what I said. And what we are dealing with has a greater impact on human behavior than knitting.

Illicit use of LSD or psilocybin, but not MDMA or nonpsychedelic drugs, is associated with mystical experiences in a dose-dependent manner - PubMed

Psychedelic drugs have long been known to be capable of inducing mystical or transcendental experiences. However, given the common "recreational" nature of much present-day psychedelic use, with typical doses tending to be lower than those commonly taken in the 1960s, the extent to which illicit...

www.ncbi.nlm.nih.gov

 

[Pup Tentacle]

Until you can prove it, YOU MAY feel like changing that thread title to something less absolute. The conclusions you draw are interesting, but seem, at best to be a hypothesis that doesn't seem to take into account a number of other factors.

 

[HeavenlyBlue]

Until you can prove it, YOU MAY feel like changing that thread title to something less absolute. The conclusions you draw are interesting, but seem, at best to be a hypothesis that doesn't seem to take into account a number of other factors.

Yes, it is a hypothesis. One that I have supported with sizable pile of evidence.

I changed the title as well.

 

[WoundedHealer]

Just because it works on the same receptors as seratonin and dopamine doesn't mean it needs to be addictive. People enjoy many sources of pleasure that require said chemicles and aren't "addicted"

 

[iorrus]

This link has been postulated to account for the anti-psychotic effect of 5-HT2a antagonists in the treatment of schizophrenia. Dopamine antagonists have been used to treat this disease.

Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action - PubMed

The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotic drugs modulate information processing in cortico-limbic circuits via dopamine D2 receptor blockade in nucleus accumbens (NAc) whereas atypical antipsychotic drugs preferentially...

www.ncbi.nlm.nih.gov

Which means nothing, I can postulate as much as I want about something it's not evidence of anything.

5-HT2a agonism has been demonstrated to cause an efflux of dopamine in the cerebral cortex.

5-HT(2A) and 5-HT(2C) receptor stimulation are differentially involved in the cortical dopamine efflux-Studied in 5-HT(2A) and 5-HT(2C) genetic mutant mice - PubMed

Both 5-HT(2A) and 5-HT(2C) receptors modulate cortical dopamine efflux, but in opposite directions. We have now compared the ability of the three 5-HT(2A/2C) receptor agonists, DOI (R(-)-2,5-dimethoxy-4-iodoamphetamine), mCPP (meta-chlorophenylpiperazine) and MK-212 (6-Chloro-2-(piperazinyl)...

www.ncbi.nlm.nih.gov

Yes dopamine is probably involved among a myriad of other factors.

5-HT2a receptors are localized in the nucleus accumbens, an area of the brain that is central to mechanisms involved with reward and addiction.

Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action - PubMed

The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotic drugs modulate information processing in cortico-limbic circuits via dopamine D2 receptor blockade in nucleus accumbens (NAc) whereas atypical antipsychotic drugs preferentially...

www.ncbi.nlm.nih.gov

So what? Just because these receptors are situated in part of the brain that is associated with reward and addiction means nothing. The brain is complex this is like trying to work out how an aircraft works by saying a passenger chair was found near to the engine.

5-HT2a receptor agonism enhances dopamine receptor (D2R) signaling.

Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes - PubMed

Ok, so dopamine receptor signalling is enhanced probably because there is an influx of dopamine as mentioned above.

When 5-HT2a receptor density is elevated, the behavioral effects of cocaine become more pronounced.

Elevated Expression of Serotonin 5-HT(2A) Receptors in the Rat Ventral Tegmental Area Enhances Vulnerability to the Behavioral Effects of Cocaine - PubMed

The dopamine mesocorticoaccumbens pathway which originates in the ventral tegmental area (VTA) and projects to the nucleus accumbens and prefrontal cortex is a circuit important in mediating the actions of psychostimulants. The function of this circuit is modulated by the actions of serotonin...

www.ncbi.nlm.nih.gov

5-HT2a receptors are also involved in cue-induced reinstatement of MDMA-seeking behaviour. Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviour - PubMed

So what this is just a load of junk thrown together. Is 5-HT2a now the primary mechanism of addiction?? We have no idea how any of this stuff works. Once again we are simply looking at the outside of an airplane noticing that water seems to move slightly quicker down the side when it is in the air versus on the ground and deducing from that that water moving over the plane makes it fly.

While withdrawal symptoms don't occur after using psychedelics, this does not mean that they do not alter reward seeking behavior. You may find yourself obsessed with integrating your experience. You may feel an afterglow, probably due to the upregulated activity of D2R following the use of psychedelics. You may find that the drug and the drug-induced state occupy your thoughts, so much that you spend many hours discussing and philosophizing about what it all means. Meanwhile, the plant from which it came is cultivated. You grow only the ones with the highest concentration of goodies. You do this for 100,000 years. You find that the drug induced state changes your behavior, even when it wears off. You feel a sense of interconectedness. You have a love for others that wasn't there before. This you attribute not to the drug, but to your voluntary thoughts. Your voluntary thoughts changed your behavior. Right?

Well withdrawl symptoms is by definition the nature of 'addiction' not necessarily natural highs which you can get by taking a shower. I mean the leap from the science to the conclusion is simply staggering, how can the fact that DMT operates on dopamine receptors lead to a conclusion about anything. In particular the type of long term highly complex changes you are referring to.

EDIT - I want you to have a quick look at this video about mRNA (in real time) making a single protein and just contemplate how complex the human body actually is.

 

[HeavenlyBlue]

It would be helpful if you would provide some peer reviewed research to justify your claims.

Symptoms of withdrawal do not always apply to behavioral addiction. However, behavior is a reflection of the physical structure of the brain.

In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [(11)C]-(+)-PHNO - PubMed

Drug addiction has been associated with deficits in mesostriatal dopamine (DA) function, but whether this state extends to behavioral addictions such as pathological gambling (PG) is unclear. Here we used positron emission tomography and the D3 receptor-preferring radioligand [(11)C]-(+)-PHNO...

www.ncbi.nlm.nih.gov

And yes, the human body is very complicated. It's fun to think about.

 

[iorrus]

It would be helpful if you would provide some peer reviewed research to justify your claims.

You've simply supplied some research regarding the action of DMT on some receptor sites and neurotransmitters and have jumped to an unjustifiable conclusion. What claims do I need to prove exactly that we have only a surface understanding of the actions and effects of neurotransmitters in the brain? I suggest you send your hypothesis to some of the authors of those papers and see what they say It's you who needs to provide the evidence as you are making an enormous claim based on very little evidence in direct contradiction of the professional opinion of countless psychologists and specialists who have worked with psychadelics.

Symptoms of withdrawal do not always apply to behavioral addiction. However, behavior is a reflection of the physical structure of the brain.

In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [(11)C]-(+)-PHNO - PubMed

Drug addiction has been associated with deficits in mesostriatal dopamine (DA) function, but whether this state extends to behavioral addictions such as pathological gambling (PG) is unclear. Here we used positron emission tomography and the D3 receptor-preferring radioligand [(11)C]-(+)-PHNO...

www.ncbi.nlm.nih.gov

Some behavior is a reflection of the physical structure of the brain.

 

[SkyKitty]

I am not sure about the title too. Psychedelics can also be frightening and cause adversions. I know many people who have tried them and found it so displeasurable or scary that they never do them again. That is just an anecdote but I never saw someone get physically sick after discontinuing psychedelics and resort to theft or sex work because they were craving psychedelics so bad that they were willing to do anything for another hit.

Now antidepressents used as prescribed on the other hand...

 

[universecannon]

Dimethyltryptamine (DMT): Prevalence, user characteristics and abuse liability in a large global s - Science - Welcome to the DMT-Nexus

you should look into what physical addiction actually is

Physical dependence - Wikipedia

en.wikipedia.org

a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms[1] of withdrawal result from abrupt discontinuation or dosage reduction.[2]

 

[Orion]

I see the points being made, I just never see it happen.

 

[HumbleTraveler]

No disrespect by any means, but I think theres a big gap here in the difference between an absolute physiological dependence and an 'addicting' experience.


Heroin addiction, that's an addiction. Hell, even cigarettes and coffee, where you physically feel like a large piece of poop sliding across earth if you dont get your fix. Thats addiction/dependence.

Riding a motorcycle, while, yes, it's an absolutely incredible feeling that can become 'addicting' and make you want to get out on it for the adrenaline rush, your body isn't like RIGHT NOW, GO ON MOTORCYCLE OR YOU'RE GOING TO START CONVULSING AND THROWING UP.

-Insert your favorite psychedelic here-, a physiological dependence... no. I could understand that the journey itself, where you go, might become something where you desire revisiting, frequently or infrequently, but being at the point where it becomes a detriment to your mental state, hiiiiiiiighly improbable.

 

[march]

If wondering is an addiction,yes psychedelics are addictive.

 

[HeavenlyBlue]

I wouldn't expect someone who has had over 4000 posts on this forum to admit that my hypothesis carries any weight.



If people don't have sex, I don't see them getting sick or ill. Sex still feels great and takes up an enormous part of waking thought.

As far as the variability of the experience: Yes, of course it happens. But ask yourself this, What are the top five moments in your life when you felt the absolute best? What moments do you recollect as most fond?

I have a feeling that almost everyone here would list any number of drug induced experiences.

 

[xram]

It seems you do not understand what "physically addictive" actually means. As others have pointed out, by the standards you are applying here, just about anything is addictive. Even the staunchest drug warriors will admit that psychedelics do NOT cause physical dependence. Indeed, they are the most useful tools we have for combatting real drug and alcohol addiction (and some of the other harmful behavior patterns you might use the term form).

Your last point has absolutely nothing to do with the drug being addictive, at all - and for many people, their experiences are so meaningful precisely because they helped them to break addictions to other drugs (look up trip reports for ibogaine).

While it's fun to be provocative and all (I'm going to give you credit and assume you're not just an idiot or a troll...), let's remember that our words actually have meanings.