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Pharmacological options in the treatment of addiction

MeDieViL

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Yada yada wheter its efford or drugs are the key or a combination of both, its all possible, dont turn this thread in another garbage discussion like that.

Ive been researching this, here's an overview of pharmaceutical compounds that can be helpfull in addiction to several drugs, for more info look up some study's, its just an overview wich can get people started.

NAC
Ibogaine
Acamprosate
Memantine
Vigabatrin
Modafinil
Topiramate
Lobeline
Wellbutrin
Magnesium
DXM
Baclofen
Rimonabant
Naltrexone
Clonidine
Tiagabine
Galantamine (or other agents increasing acetylcholine content)
Kappa agonists/antagonists
Serotogenics
Ondansetron
Varenicline
Oxcarbazepine
Disulfiram
Gabapentin
Pregabalin
Buprenorphine

(ment to say pharmaceutical options in the title)
 
So what type of discussion should this be about? So far you've provided a list of drugs with no accompanying information or dialogue.
 
So what type of discussion should this be about? So far you've provided a list of drugs with no accompanying information or dialogue.

This is just for informational purposes, i can provide all references too if ppl are interested, this could turn in a interesting discussion about the mechanisms behind addiction and how those agents could help.
 
I don't get it.........the self-treatment of addiction is a slippery slope.

If well informed and sincere, i believe that the best way to" get off" opioids (and depressants; this is more complicated) is to willingly titrate down as slow as needed, with an excess supply of the drug in question (reduces fear of 'running out', and forces one to practice self-control. I am, generally, not an advocate for forced, intervention mandated, inpatient" rehab". Addicts of stimulants may benefit from psychological support, as these individuals often have underlying psychiatric disorders. 30 day rehabs are not a good approach to physiologic dependence.

You failed to mention methadone. I personally found methadone maintenance to be the best route......i took total control of my withdrawal, never told the clinic, and by the time i stopped, i had accumulated thousands of 10mg methadone tablets. I think its long term efficacy at treating withdrawal is superior to that of buprenorphine; no unpleasant "induction", high bioavailability, more predictable and straightforward pharmacology-kinetics etc. Unfortunately, methadone is perhaps the most "controlled" and stereotyped of the opioids.
 
Rehab have only a long term succes rate of 1/3 with 2/3 of the ppl relapsing, pharmaceutical options reduce the chances of relapse, they are also capable of making ppl use less drugs because they interfere with several pathways implicated in addiction.
As an example they can reduce craving and other stuff.

Getting of the drug yourself, does work, but only for 1/3th long term, so its definatly not the best option at all, and pharmaceutical options cant be ignored.
 
Indeed i should have added methadone to the list.

perhaps I have to disagree. Methadone provides a legal and efficient replacement for illicit opiates, but I've yet to come across a convincing argument for its value in the treatment of addiction.

Personally, I've had to discontinue methadone treatment on close to a dozen occasions because it's just so damn pleasant--even after months of daily use. The passage in which Odysseus' crew members are slowly lured to their deaths by the wicked Sirens comes to mind...
 
AFAIK it has been shown to eliminate alot of issues related to addiction (like crime and other stuff) will need to check out the study's again.

Its one of the way to treat addiction, either substitution therapy, or substances that 1 supress withdrawals and 2 eliminate craving.

Personally im interested in agents that reduse my intake of dexedrine, i dont have tolerance or depedency issues, however i cant use it therapeutically as i only binge on it.
 
Another big component of addiction is impulsivity, thus pharmaceuticals that help this are also options in certain types of addiction.
 
Agents that target the alpha3beta4 receptors are a very interesting option, some references:
Eur J Pharmacol. 2008 Dec 3;599(1-3):91-5. Epub 2008 Oct 1.
Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration.
Glick SD, Sell EM, Maisonneuve IM.

Center for Neuropharmacology and Neuroscience, Albany Medical College (MC-136), 47 New Scotland Avenue, Albany, NY 12208, USA. [email protected]
Abstract
The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the self-administration of several drugs of abuse. Previous work has established that 18-MC is a potent antagonist at alpha3beta4 nicotinic receptors. Because high densities of alpha3beta4 nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine self-administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine self-administration. Similar results were produced by local administration into the same brain areas of two other alpha3beta4 nicotinic antagonists, mecamylamine and alpha-conotoxin AuIB. Local administration of 18-MC, or the other antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine self-administration. In contrast, local administration of 18-MC and the other antagonists decreased sucrose self-administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving alpha3beta4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose self-administration.

Eur J Pharmacol. 2004 May 25;492(2-3):159-67.
Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration.
Pace CJ, Glick SD, Maisonneuve IM, He LW, Jokiel PA, Kuehne ME, Fleck MW.

Center for Neuropharmacology and Neuroscience, The Albany Medical College, MC-136, 47 New Scotland Avenue, Albany, NY 12208, USA.
Abstract
18-Methoxycoronaridine, a novel iboga alkaloid congener, reduces drug self-administration in animal models of addiction. Previously, we proposed that these effects are mediated by the ability of 18-methoxycoronaridine to inhibit nicotinic alpha3beta4 acetylcholine receptors. In an attempt to identify more potent 18-methoxycoronaridine analogs, we have tested a series of 18-methoxycoronaridine congeners by whole-cell patch clamp recording of HEK 293 cells expressing recombinant nicotinic alpha3beta4 receptors or glutamate NR1/NR2B N-methyl-d-aspartate (NMDA) receptors. The congeners exhibited a range of inhibitory potencies at alpha3beta4 receptors. Five congeners had IC(50) values similar to 18-methoxycoronaridine, and all of these were ineffective at NMDA receptors. The congeners also retained their ability to reduce morphine and methamphetamine self-administration. These data are consistent with the importance of nicotinic alpha3beta4 receptors as a therapeutic target to modulate drug seeking. These compounds may constitute a new class of synthetic agents that act via the nicotinic alpha3beta4 mechanism to combat addiction.

Synapse. 2007 Jul;61(7):547-60.
18-MC acts in the medial habenula and interpeduncular nucleus to attenuate dopamine sensitization to morphine in the nucleus accumbens.
Taraschenko OD, Shulan JM, Maisonneuve IM, Glick SD.

Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA. [email protected]
Abstract
18-Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, is a potential treatment for drug addiction. 18-MC has been shown to decrease self-administration of drugs (e.g., morphine, methamphetamine, nicotine) and attenuate opioid withdrawal in rats. In previous studies, systemic pretreatment with 18-MC abolished the sensitized increase in accumbens dopamine levels induced by chronic morphine administration. In vitro studies have shown that 18-MC is a potent antagonist of alpha3beta4 nicotinic receptors, and alpha3beta4 antagonism is believed to be the primary mechanism responsible for 18-MC's effects on drug self-administration and possibly on morphine-induced changes in mesolimbic dopamine. While there are very low densities of alpha3beta4 nicotinic receptors in the mesolimbic pathway, these receptors are prominently localized in the medial habenula (MHb) and in the interpeduncular nucleus (IPN). These nuclei and the habenulo-interpeduncular pathway connecting them are believed to function as part of an alternate reward pathway modulating the dopaminergic mesolimbic pathway known to be involved in drug addiction. In the present study, to determine if 18-MC acts in the MHb or in the IPN, the effects of local infusion of 18-MC into these brain areas were assessed on mesolimbic dopamine responses to acute and repeated morphine treatment. Administration of 18-MC (10 mug) into either the IPN or MHb blocked the sensitized dopamine response to repeated morphine in the nucleus accumbens; 18-MC had no effect on the dopamine response to acute morphine. The results suggest that 18-MC acts in the habenulo-interpeduncular pathway to modulate the effects of repeated morphine in the dopaminergic mesolimbic system.

Eur J Pharmacol. 2005 Nov 21;525(1-3):98-104. Epub 2005 Nov 10.
Attenuation of morphine withdrawal signs by intracerebral administration of 18-methoxycoronaridine.
Panchal V, Taraschenko OD, Maisonneuve IM, Glick SD.

Center for Neuropharmacology and Neuroscience MC-136, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
Abstract
18-Methoxyroconaridine (18-MC), a synthetic derivative of ibogaine, reduces morphine self-administration and alleviates several signs of acute opioid withdrawal in rats. Although there is already well documented evidence of the mechanism mediating 18-MC's action to reduce the rewarding effects of morphine, nothing is known about the mechanism responsible for 18-MC's attenuation of opioid withdrawal. In vitro studies have demonstrated that 18-MC is a potent antagonist of alpha3beta4 nicotinic receptors (IC50=0.75 microM), which are predominantly located in the medial habenula and interpeduncular nuclei. Previous work indicating that alpha3beta4 nicotinic receptors mediate 18-MC's effects on drug self-administration prompted us to assess whether brain areas having high or moderate densities of alpha3beta4 receptors might be involved in 18-MC's modulation of opioid withdrawal. To test this possibility, 18-MC was locally administered into the medial habenula, interpeduncular nucleus and locus coeruleus of morphine-dependent rats; this treatment was followed by naltrexone to precipitate a withdrawal syndrome. Pretreatment with various doses of 18-MC into the locus coeruleus significantly reduced wet-dog shakes, teeth chattering, burying and diarrhea, while pretreatment into the medial habenula attenuated teeth chattering, burying, and weight loss. Some doses of 18-MC administered into the interpeduncular nucleus significantly ameliorated rearing, teeth chattering, and burying, while other doses exacerbated diarrhea and teeth chattering. The present findings suggest that 18-MC may act in all three nuclei to suppress various signs of opioid withdrawal.

Eur J Pharmacol. 2005 Apr 25;513(3):207-18. Epub 2005 Apr 14.
Is antagonism of alpha3beta4 nicotinic receptors a strategy to reduce morphine dependence?
Taraschenko OD, Panchal V, Maisonneuve IM, Glick SD.

Center for Neuropharmacology and Neuroscience MC-136, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA. [email protected]
Abstract
18-Methoxycoronaridine, a synthetic iboga alkaloid congener, has been previously shown to attenuate several signs of morphine withdrawal in rats. The recently discovered action of 18-methoxycoronaridine to block alpha3beta4 nicotinic receptors may be responsible for this effect. To test this hypothesis the effects of non-selective alpha3beta4 receptor antagonists, dextromethorphan, mecamylamine, bupropion, and their combinations, were assessed on of acute naltrexone-precipitated (1 mg/kg i.p.) morphine withdrawal in rats. Dextromethorphan (5-40 mg/kg, s.c.), mecamylamine (0.25-4 mg/kg, i.p.) and bupropion (10-30 mg/kg, i.p.) alone produced variable effects on signs of withdrawal. However, two low-dose combinations, i.e., dextromethorphan (5 mg/kg, s.c.) and mecamylamine (0.25 mg/kg, i.p.), mecamylamine (0.25 mg/kg, i.p.) and bupropion (10 mg/kg, i.p.) as well as the three-drug combination significantly attenuated diarrhea and weight loss; none of the agents administered alone had these effects. The results of the present study provide evidence that alpha3beta4 nicotinic receptors are involved in the expression of at least two signs of opioid withdrawal.

Those have been reported to make ppl feel more satisfied with lower doses of drugs without a constant need for more, thus look most promosing for my type of addiction.
 
For other ppl, massive tolerance combined with severe withdrawal issues is the biggest issue in their addiction, in those cases nmda antagonists can be of most benefit.

Then for others its self medication as the root cause, etc etc.

Etc, i'm compoling alot of data to put togheter in this thread.
 
I found this very interesting, this is basicly substitution therapy combined with something that blocks the euphoric and reinforcing effects of the substitution.
ur Neuropsychopharmacol. 2007 Dec;17(12):781-9. Epub 2007 Jul 3.
Comparing and combining gamma-hydroxybutyric acid (GHB) and naltrexone in maintaining abstinence from alcohol: an open randomised comparative study.
Caputo F, Addolorato G, Stoppo M, Francini S, Vignoli T, Lorenzini F, Del Re A, Comaschi C, Andreone P, Trevisani F, Bernardi M; Alcohol Treatment Study Group.

G. Fontana Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. [email protected]
Abstract
Maintaining abstinence from alcohol is the main goal in treating alcohol dependence. Our aim was to evaluate the efficacy of gamma-hydroxybutyric acid (GHB) and naltrexone (NTX), and their combination in maintaining abstinence. Fifty-five alcoholics were randomly enrolled in three groups and treated for 3 months with GHB, GHB plus NTX, and NTX, respectively. At the end of treatments, abstinence was maintained by 13 patients (72.2%) in combination group, 8 patients (40%; P=0.03) in GHB group, and one patient (5.9%; P=0.0001) in NTX group. Relapses in heavy drinking tended to occur more frequently in GHB group (15%) than in either combination group (no cases) or NTX group (5.9%), but such differences were not statistically significant. The GHB/NTX combination was more effective than either drug given alone; this suggests that the two drugs combine their different actions synergistically without suppressing the favourable effects of each other.
Pharmacol Res. 2008 Apr;57(4):312-7. Epub 2008 Mar 14.
An open randomized study of the treatment of escitalopram alone and combined with gamma-hydroxybutyric acid and naltrexone in alcoholic patients.
Stella L, Addolorato G, Rinaldi B, Capuano A, Berrino L, Rossi F, Maione S.

Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Faculty of Medicine and Surgery, Second University of Naples, Naples, Italy. [email protected]
Abstract
gamma-hydroxybutyric acid (GHB) and the selective serotonin reuptake inhibitor escitalopram are effective in inducing and maintaining abstinence in alcohol. Naltrexone (NTX), an opioid antagonist, may be effective in preventing relapse in alcohol-dependent subjects. To evaluate whether each drug and its combination help to maintain alcohol abstinence, we determined the relapse rate over 6 months in 3 groups of patients. Group 1 (11 patients) received escitalopram (20 mg/day) orally administered; group 2 (12 patients) received NTX (50 mg/day) and escitalopram (20 mg/day); group 3 (12 patients) received GHB (75 mg/kg body weight) and escitalopram (20 mg/day); and group 4 (12 patients) received NTX (50mg/day) plus GHB (75 mg/kg) and escitalopram (20 mg/day). All groups received psychological support and underwent urine tests for alcohol metabolites twice a week. In group 1 (escitalopram only), 6 patients relapsed within 3 months and 3 after 6 months; whereas 2 patients remained abstinent. In group 2 (SSRI+NTX), 5 patients relapsed after 3 months and 3 after 6 months; whereas 4 patients remained abstinent. In group 3 (GHB+SSRI), 3 patients relapsed after 3 months and 3 after 6 months; whereas 6 patients remained abstinent. Finally, in group 4 (NTX+GHB+SSRI), 1 patient relapsed after 3 months and 1 after 6 months, whereas 10 patients remain abstinent. In conclusion, the combination of NTX+GHB+SSRI was the most effective in preventing relapses.
The succes rate of this is very high, amphetamine+naltrexone for meth addiction may be an alternative, an opiate+naltrexone wont work but perhaps the addition of rimonabant produces comparable results.
 
perhaps I have to disagree. Methadone provides a legal and efficient replacement for illicit opiates, but I've yet to come across a convincing argument for its value in the treatment of addiction.

Personally, I've had to discontinue methadone treatment on close to a dozen occasions because it's just so damn pleasant--even after months of daily use. The passage in which Odysseus' crew members are slowly lured to their deaths by the wicked Sirens comes to mind...

I was maintained on methadone for a 3 or so years at 380mg/day. My clinic was extremely high-end, in the penthouse of a Beverly Hills hospital (the hospital itself is actually pretty shitty). It was ultra-private, no patients ever saw another, it was geared for high-profile patients who wanted great anonymity. It was quite expensive, paid in cash (don't want that shit on my insurance record), and very liberal with the dose (which is how I got to 380mg, yes, 38 10mg tablets per day which was actually getting me high as fuck). They did drug tests, but if you failed, they didn't care (I was using benzos, sometimes some ultra-high doses of fentanyl or heroin, and some cocaine here and there). Towards the end I was only going once every THREE months, which means bottles upon bottles of 10mg methadone tablets.

My point is, they gave me as much methadone as I wanted (again, for a hefty price, but I was fortunate to have the means....~$2,000 a month is a lot cheaper than heroin), so much so that I became "bored" with it, and felt the inevitable lengthy nod that 380mg of methadone causes was "no longer necessary". I slowly began tapering (without telling the clinic, i'd come every 3 months for my massive amount of pills....hey I was paying $2,000 for what is technically a cheap drug, why not get the 38 pills/day), and after around a 14 months, I wrote them a letter saying that I no longer needed their services. Again, I went at a pace comfortable to me, and finally went "cold turkey" at 1/4 of a 10mg tablet (2.5mg). This was the most unpleasant part, but lasted all of 12 days. It was honestly trivial compared to cold turkey heroin withdrawal (ultra-intense, open-eyed visual hallucinations etc), and didn't even come close to benzo withdrawal. Even though I still had thousands of extra methadone tablets I felt no "lure" or "craving" for the drug. I actually used alot of the tablets for my two dying dogs (canines are poor metabolizers of methadone, and need large doses).

Bottom line..........its unfortunate how "rigid" our methadone maintenance laws, and one shouldn't have to pay $6,000 for a 3 month supply. The drug can be without question abused (I would still rank it among my top 5 opioids for recreation), and yes, can also result in acute toxicity fatalities in the non-tolerant individual. But, it is technically, cheaper than buprenorphine, is a pure-agonist and NMDA-antagonist, and requires no unpleasant induction-precipitated withdrawal, and is extremely predictable. Those who have had "bad" experiences with methadone are those who have been abruptly "cut off" or "disciplined" by low end clinics which strictly adhere to the law, and require humiliating lines, drug tests, etc (I experienced this in Australia, I went to a state run methadone clinic, and it was very humiliating). Personally, I feel as though "disciplining" a patient by withholding or reducing a dose to illicit withdrawal to be a very real form of torture/gross malpractice.

The DEA has made buprenorphine extremely easy to prescribe for addiction (a elementary "DATA 2000" waiver; 8-hour "test"), yet in order to open a methadone clinic, one must go through overly extensive regulatory red-tape.

When used properly, methadone is a great drug for getting off of opioids, or staying on them until you feel it is necessary. Access and "celebrity" treatment should not cost $2,000 (actually more with deliveries, $400 a pop) given the ultra-low cost of methadone's production. My clinic never did psychotherapy or anything unrelated to dispensing methadone. At a normal methadone clinic I probably would not have excelled as I did. To be sure, drug laws are very prohibitive in respect to methadone. Personally, I admit that I prescribe it less than I probably should (for pain only, I am not licensed to prescribe methadone for addiction......yet I am able to write bupe scripts for addiction). The fear associated with "over-prescribing" methadone is a real one; the DEA would thinking I am running some unlicensed methadone clinic if I prescribed it as much as I felt it was needed (again, I do not work in addiction medication, I am an a rather 'green' anesthetist and do not have a secondary "chronic pain").

The simple truth..........methadone is valuable too, but is too hard to access........

In regards to d-amphetamine tolerance reduction...........what dose and ROA are you using?

My point is, they gave me as much as I wanted, and eventually I realized......
 
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In my opinion should consist of:

- Agents that prevent tolerance from occuring
- Agent that atenuates withdrawals
- Agent that inhibits craving
- Substitution with a simular drug that isnt problematic in low daily doses, eventually combined with low dose naltrexone to atenuate its reinforcing effects.

Why something to prevent tolerance? Every addict can relapse under some conditions and avoiding him by going in the tolerance addiction cycle allways him to easily should stop taking it again, when there's also a anticraving pharmaceutical.

We also have to keep in mind some individuals will allwayse euphoria, and substituton wich a mild euphoric agent could be something ideal for those cases that get addicted over and over and over again.
 
In my opinion should consist of:

- Agents that prevent tolerance from occuring
- Agent that atenuates withdrawals
- Agent that inhibits craving
- Substitution with a simular drug that isnt problematic in low daily doses, eventually combined with low dose naltrexone to atenuate its reinforcing effects.

Why something to prevent tolerance? Every addict can relapse under some conditions and avoiding him by going in the tolerance addiction cycle allways him to easily should stop taking it again, when there's also a anticraving pharmaceutical.

We also have to keep in mind some individuals will allwayse euphoria, and substituton wich a mild euphoric agent could be something ideal for those cases that get addicted over and over and over again.
Also while things like naltrexone work against the reinforcing effects many drugs, they actually still leave alot euphoria available of many drugs.

All those options look pretty promosing for me.
 
But we would still need a part of the puzzle, the chasing for euphoria makes an addict lose intrest in other tasks, in case of amphetamine i beleive that is because balance is way to shifted to the nucleus accumbens, theoretically with naltrexone we can shift dopaminergic balance to more motivational structures, shifting balance away from the nucleus accumbens, ideal for people that want to be productive on amp instead of being lazy, check this experience:
Naltrexone reduces the craving to various substances, including GHB and uppers. You can find out more by googling it. It won't reduce the high to stimulants, but anxiolysis / euphoria from GHB to some extent.
So its possible to keep alot of the mood boost, therefor its a combination i would want to try, just not because i take too much amp, but because i take it for adhd but i still dont give a shit about things.
 
I definatly think that reversing tolerance and then let someone withdrawn from a drug is insufficient, after that we will have to find out wheter there's anything wrong with the patient wich he self medicates for, after that initiate treatments to control craving and then wich may be controversial add in something like memantine to prevent tolerance afer taking a drug again, would understand they wonna keep using drugs recreationally, then disrubting the tolerance and dependency cycle is of crucial importance and with a anti craving a compounds chances are alot bigger it will stay with a ocasion.

And the mild substitution is good imo (eventually with naltrexone to block the euphoric and reinforcing effects of that, as works with GHB and alcohol), if they constantly dont feel like they lose what they liked, even tough its a minimal, they may be more satisfied.

So far my ramblings on amp.
 
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i'm using naltrexone to try to stay off alcohol.. from your research, if i am to take 50mg everyday or just when i feel the urge to drink, could it help me?
 
wesley have you tried the naltrexone and amphetamine combo yet? i want to kno how it works out.


i too have the same problem. amphetamines give me excessive euphoria without much motivation. prob related to excessive mesolimbic stimulants are less mesocortical.
 
wesley have you tried the naltrexone and amphetamine combo yet? i want to kno how it works out.


i too have the same problem. amphetamines give me excessive euphoria without much motivation. prob related to excessive mesolimbic stimulants are less mesocortical.

I have a report of someone that tried it:
Hi!

It won't reduce the euphoria of amp IMHO and GHB felt ok too. You will have to try it out first.
So apperantly the naltrexone doesnt supress the euphoria of other drugs to much while inhibiting the reinforcing effects, this explains the high succes rate's in the GHB/naltrexone study's, looks like a very promosing avenue in the treatment of addiction imo.

Nope didnt try it yet but will soon.
 
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