View Full Version : TCAs as opioid agonists?

09-12-15, 12:32 PM
Anyone know anything about this and able to explain it in simple English?

Also, anyone know of any other psych meds that activate opioid receptors?

09-12-15, 01:17 PM
Zuzu? Tyger? Kunga? SB?? (now I'm desperate) :lol:

09-12-15, 01:57 PM
I think they tend to hit sigma receptors if I remember right, which ties into the dopamine system pretty directly. Not sure how strong the effect is considering all the other receptors they interact with. Almost all therapeutic drugs are pretty dirty in that they hit a bunch of related systems at once. The fact that the dirtier meds seem to work better than the more specific drugs is a pretty clear indicator 1) that the brain is a pretty complex system and 2) that we really have a poor understanding of which systems are primarily involved with which disorders/meds.

09-12-15, 03:52 PM
I sprained my ankle.

Tramadol makes me happy.

Not just undepressed like Celexa, but euphoric, but not in a bipolar hypomanic way.

I can work. I feel so happy.

09-12-15, 03:52 PM
It's better than alcohol even.

09-12-15, 04:23 PM
I had a very bad asthmatic attack on amitriptyyline which lead to my first dog dying - wife lost control.
Hard to forget

Opiates (cf PNS) -
opiates lead to respiratory depression

PNS agonism (if antagonists are used to treat asthma) do too.

So - makes sense to me that TCas could operate through the opiate system.

09-12-15, 04:38 PM

Here is an interesting read.

09-12-15, 04:47 PM
Thanks Tyger, SB and Hound.

09-12-15, 04:51 PM
I don't want a painkiller.

I want something that behaves like an (opioid) painkiller to use as an antidepressant.

09-12-15, 06:32 PM
I don't want a painkiller.

I want something that behaves like an (opioid) painkiller to use as an antidepressant.

I googled "buprenorphine for depression", but I am not layhumanly familiar with this specific link or author.

A: Buprenorphine is an only mildly abuse-liable drug that is occasionally dramatically helpful in treating depression that does not respond to conventional treatments, even including ECT and MAOIs. - See more at:

09-13-15, 02:22 AM
That's interesting.

The familial coaggregation of ADHD+PTSD disorders suggests that these disorders share familial risk factors and that their co-occurrence is not due to diagnostic errors.Causes of depression
( (PTSD)

If depression is a 'slowing' down of the system - narcotic - endogenous opioid - pain-relief - then 'speeding' the system should alleviate depression ( -

ie re-balancing the SNS with PNS, endogenous stimulant with endogenous narcotic.


It is not currently known why only a proportion of people acquire PTSD on traumatic experience.Sensitive people would be more likely to acquire PTSD


PTSD - an environment of particular extreme insensitivity with sensitivity (ADHD) immersed.

What happens when sensitivity is exposed to insensitivity ?
Interassociated memories of trauma connect ie 'place of abuse' becomes linked to (drives a stress response in the indivdual) 'actual (stressful) abuse'.
ie (
PTSD patients with reduced hippocampal volumes lose the ability to discriminate between past and present experiences or interpret environmental contexts correctly. Their particular neural mechanisms trigger extreme stress responses when confronted with environmental situations that only remotely resemble something from their traumatic past. This is why a sexual assault victim is terrified of parking lots because she was once raped in a similar place. A war veteran still cannot watch violent movies because they remind him of his trench days; his hippocampus cannot minimize the interference of past memories.What does the abuse -> depression victim need to do ?

People think that memory is a good thing - but assess history and it's filled with hideous characters, terrible wars and wholly pointless killing; is it good for one's mental health to remember ?

General comment - as long as we're fixed in a rational moral state - wouldn't it be good to be able to forget the major motifs of man (war/competition) over evolution (war/competition) ?

Why would this (ie memories correlated with trauma) cause depression ?
Chronically triggered - ie heightened cortisol reaction.

Causes of depression


Don't like the idea that

anxiety (this should be heightened SNS) and depression (this should be heightened PNS activity) travel together ... ... ... but then again stress (cortisol/SNS at the level of adrenal glands) and


reactive stress-relief ie elevated PNS activity should travel together.

Homeostatic re-balancing (because that's what physiology does) of the set-point of SNS/PNS balance.

Good - the relationship of male (+) to female (-) archetype is complementary and not antagonistic.

Intelligent technology can set you free (

eg mumsnet (
Causes of depression (
7.Social isolation

No clothes washing, no ironing, no mopping, no dusting, no bathroom cleaning, no dish washing, no cooking, no nuttin' ... ... even if that means having 1 set of quick drying clothes which you wash in at the local gym and have no possessions on a raw vegan (no processing/preparation required) diet.

Job done.


Causes of depression (


Certain medications.
Conflict. [distress = being forced to act in an irrational/immoral way - this is not in keeping with mind]
Death or a loss ['attachment' to 'detachment' social evolution in the human lifecycle - everyone dies - the goal is to live before you die]
Genetics - [see [epigenetic predisposition to] sensitivity (cf ADHD) argument above]
Major events. [distress -> unknown - cannot leverage cerebellar automatising functionality ie operate on auto-pilot; I hate doing anything that I don't know how to do]
Other personal problems.

Serious illnesses. [-> physiological ie distress]
Substance abuse. [see Peripheral - rat park - attraction to opioids in distressful environment - substance abuse secondary and then re-inforces physiological disruption]


The general point that stupid human beings are culpable in defining their own depression-courting milieu; or it's all environmental.

09-13-15, 03:11 AM
What does the abuse -> depression victim need to do ?
FORGETThis idea leads into ECT.

[1] Instead of cognitive pain (being forced to act immorally/irrationally) - take a less subjective form of pain - phantom limb pain.
[2] What do we want to do ? To forget the painful connectins - to discard maladaptive memories.

One way - far from ideal:
[3] 3.2.5. Electroconvulsive Therapy A case report of positive outcome has been published even though the mechanism and role of ECT relative to PLP is not well understood
[4] How would we re-characterize mal-adaptive memories ? eg the existence of war in the evolution of man giving rise to the stress response
- to superimpose a model of understanding which places primitive behaviour as a necessary transitory period in the process of the species growing up.
To extend understanding holistically will mean that memories lose their mal-adaptive distress driving aspect.


Primacy of reason (

Kant now claims to have discovered the supreme principle of practical reason, which he calls the Categorical* Imperative. (More precisely, this principle is an imperative for finite beings like usWhy does Kant use the word 'practical' ?
Because it's rooted (Kant - phenomenological not noumeological) in reason from the perspective of man.
It's not a divine (noumenology) - but a human-centric (phenomenology) ie logical sense crossed with human wellbeing.
Not just logical - as that doesn't mean anything to man.
We need what's logically best for human wellbeing.

* Back around to Kant's categories ie organized structure of mind ->- which should take us post-mind into the derivation of mathematics ( cf Stabile.

Category theory formalizes mathematical structure ( and its concepts in terms of a collection of objects and of arrows (also called morphisms (

So - see comments relating to AND (all inclusive) mind vs EOR (exclusive) mind.

ie X can feel Y EOR Z (locally logically consistent) or X can feel Y AND Z (globally logically consistent transcending maladaptive locally consistent but globally inconsistent models of understanding).

The model echoes the individual's world view.


Note connection between individual X can feel Y AND Z and homeostasis ie balanced duals (eg SNS and PNS) and disease individual X can feel Y EOR Z

... ... ... leading us finally back to ... ... ...

Dominance of SNS (anxiety) or PNS (depression) and need to correct antagonise or agonise TCAs as opioid agonists the appropriate system - in order to restore balance.

09-13-15, 03:21 AM
I must be really sleep deprived and overworked, because SB I'm actually finding your theories mildly interesting :) :p

09-14-15, 10:56 PM
naltrexone has had some interest

09-15-15, 04:26 AM
I forget how tramadol works but I know when I was prescribed it my pharmacy flagged it because there was a life threatening interaction with my other meds that popped up in their computer.

09-15-15, 04:58 AM
Yeah with Cymbalta.

I'm taking a risk taking it with Celexa.