I was looking around and saw there is some research showing opiates are effective for treatment resistant depression.
ALKS-5461 is a mix of an opiate agonists and antagonists. I get the impression the drug combo is designed to affect the opioid receptors involved in depression without affecting the ones that get you high (I think those are the mu receptors). Apparently the drug was so effective for depression it was fast tracked after stage II, and is now in stage III trials. I think (this could be in reference to another study) a group of 32 people with treatment resistant depression was tested with the drug, and all 32 improved.
I don’t understand much about the opioid receptors, although I know there are about 4 different types plus all the subtypes. Is blocking the kappa receptor considered a well researched method of alleviating depression and anxiety, and is it strictly the kappa that has antidepressant effects? Is the Mu receptor the only one that gets you high and addicted (and as a result the one that these drugs are designed to avoid activating)?
My depression is mostly under control via therapy but I know a lot of people are dealing with this shitty disease.
While I’m on the subject, are there opioids for chronic pain that don’t get you high or addicted? How do those work?
Opiates can work wonders for depression, but I question how well it works without mu. Also, after a while you build up a tolerance and need more and more of the drug - which eventually will lead to GI Problems, hearing loss, ruin your testosterone levels, and make it difficult to have an erection. It appears to me that it is the euphoric effects that help the depression. Long term opiate use is also associated with high rates of unemployment. In other words - you won’t be miserable - as long as you have a supply, but you won’t be productive either. This comes as a surprise to some - as opiates make them more productive (at least initially) - after a while - this too fades. The good things about opiates disappear with time - the bad things don’t.
Every opiate I know of can be abused by someone. Even tramadol - long considered a “safe” opiate was rescheduled this year after people finally realized how much abuse was going on. There is also a very weird side effect to opiates called opiate induced hyperalgesia. It basically causes people to have pain - often where they were originally trying to fix with the opiate - when they come off the drug. This of course makes people believe even more that the opiates are working. When they either on purpose - or by accident - stop taking one - the pain gets worse - and they think “I really need these things - look how bad I feel when I stop”. The thing is - if they did stop - some would find after a few days their pain would disappear entirely. It appears to me that both the hearing loss aspect and the hyperalgesia (and sometimes the testosterone) are not well known to some doctors.
Many people with treatment resistant depression - know they are treatment resistant - well cause they have been on ADs for a while.
I went through virtually every type of AD - over the course of years - until a doc finally suggested trying an MAOI. Parnate and Nardil worked wonders for me, while the other types of ADs did nothing. Adderall too (not prescribed for the depression). Many of the concerns about MAOIs appear to be overblown. Unfortunately - it too passed, but I suffered no long term effects from it - and it isn’t generally considered addictive.
People with chronic pain who are receiving the correct dose of opioids do not feel “high” when they take their medication. I’ve been using the same dose for about 10 years and haven’t had to increase it and don’t want to.
If you use an opioid for a while, you will become physically dependent on it. In other words, your body will notice if you don’t take it, and you will feel ill. This can be handled by slowing titrating down and taking medication to help with the symptoms of withdrawal. Dependence is biological.
Addiction is a different matter altogether from dependence – it is a psychological need for the drug.
You can have both dependence and addiction. You can have just addiction. You can have just dependence.
How does the chemistry of the various receptors play a role in addiction or getting high? I don’t know a lot about it, I just started reading it today but I get the impression the mu receptor plays a big role in the euphoric high as well as addiction. But there are several subsets of that receptor.
There has been some research on NMDA antagonists to prevent or reverse physical dependence and tolerance of opioids but I don’t know if any consumer products are out because of it. There was work on an opioid combined with low dose DXM as a pain drug, I’m not sure what happened with it.
I’ve been told that DXM is used as a booster for opioid painkillers for people like burn patients, who would otherwise need dangerously high doses over long periods of time. Dextrometorphan is the stereoisomer of levomethorphan; only the latter has an opiate-like effect. The former is classed as a dissociative. I’m not a chemist, so I couldn’t tell you more than that.
Ketamine, also an NMDA antagonist, is currently in trials for treatment-resistant depression. I’m also unsure of the mechanism here – although that might be because no one else knows either – but anecdotally, DXM can be used recreationally, I gave it a shot in college, and it did seem to whack my brain back into shape for a couple of weeks afterwards. It’s not a very practical method of taking care of the problem at present, but perhaps the research will someday yield a solution that wouldn’t have the patient stumbling into walls and staring intently at the irregular texture of gravel as they tried to go about their day.
I might also observe that if you have depression co-morbid with some kind of anxiety disorder, hammering the anxiety into submission can do wonders for your mood. A nasty part of the depression cycle is feeling too overwhelmed to do anything, not getting anything done, watching it pile up until you feel too overwhelmed to do anything, etc. A tranquilizer or anxiolytic paradoxically makes you more productive, at least in the short term, by making the initial problem you need to tackle seem like no big deal after all.