# Pramipexole



## rawrguy (Mar 29, 2008)

Lately I have been on 3.0mg of Pramipexole, a dopamine agonist used to treat Parkinson's Disease, and I've gotta say it's awesome. My social inhibitions are waay lower, I would even say they are close to gone. So far I have been on Pramipexole for 3 months on 3 different doses. The main thing with pramipexole is when you first start the medication, your dopamine shoots straight down, especially if you go straight to higher doses like I did. Side effects during the first four weeks include:

Nausea
panic attacks whenever you go out
depression
(heavy) sedation
apathy
akathesia

Today, I'm in sort of a constant euphoric state, expecially when I work out or take a cold shower (both proven to work against depression). I don't feel any sort of social "invincibility" like one would on amph or really any other stimulant, but it's enough to make me enjoy social situations and not feel completely drained at the end of the day. I also seem to be more irritable, but it's not that bad. I've been visiting my old school mates and so far there's been no problems with social interactions. Also, I do not suffer from any side effects other than a messed up sleeping schedule, insomnia, and an increased libido. I'm still testing it out whenever I go out.
Now, it would be great if crayzyMed or rocknroll714 post some Pubmed studies here regarding pramipexole and depression here:

*VVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVVV*


----------



## Noca (Jun 24, 2005)

http://www.ncbi.nlm.nih.gov/pubmed/10984002?dopt=Abstract


----------



## crayzyMed (Nov 2, 2006)

*Pramipexole*



> Comparison of pramipexole, fluoxetine, and placebo in patients with major depression.
> Corrigan MH, Denahan AQ, Wright CE, Ragual RJ, Evans DL.
> 
> Pharmacia & Upjohn, Inc., Global Clinical Research, Bridgewater, NJ 08807-0995, USA.
> Pramipexole, a dopamine D2 receptor agonist, was tested in 174 patients with major depression, with or without melancholia and without psychotic features. Three daily dose levels (0.375 mg, 1.0 mg, and 5.0 mg) were compared to fluoxetine (Prozac) at 20 mg and placebo in a randomized, double-blind, parallel-group study. After a 1 week placebo run-in period, patients were treated for 8 weeks, had a post-study follow-up (week 9), and were evaluated primarily with the Hamilton Psychiatric Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinician's Global Impressions-Severity of Illness scale (CGI-SI). All patients who received one dose of study medication were included in the observed-case analysis (no missing data were replaced). *Results indicated that by endpoint (week 8), patients receiving pramipexole at the 1.0 mg per day dose had significant improvement over baseline compared to the placebo group by measure of the HAM-D, MADRS, and CGI-SI. Significant improvement in this dose group was seen at other timepoints as well. The most obvious improvement was seen in the pramipexole 5.0 mg group, although a substantial dropout rate for this group precluded statistical tests vs. placebo late in the study. *Patients taking fluoxetine also showed significant improvements at endpoint on the MADRS and earlier in the study on the HAM-D. No new or unusual safety concerns were generated during this study. Pramipexole helped safely alleviate the symptoms of depression at 1.0 mg per day and especially in those patients who could tolerate the escalation to 5 mg per day.





> Pramipexole in treatment-resistant depression: a 16-week naturalistic study.
> Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB.
> 
> Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa, Italy. [email protected]
> OBJECTIVE: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2-D3 dopamine agonist, in patients with drug-resistant depression. METHODS: The study sample consisted of in-patients with major depressive episode, according to the DSM-IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a > 50% reduction of the Montgomery-Asberg Depressive Rating Scale (MADRS) total score and a score of I or 2 on the Clinical Global Impression scale (CGI-1) at endpoint. Side-effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). RESULTS: Thirty-seven patients were enrolled. Of these. 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses. 19 completed the 16-week follow-up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 +/- 8.4 at baseline to 13.9 +/- 11.5 at endpoint (p < 0.001) and the CGI-S decreased from 4.6 +/- 0.8 at baseline to 2.8 +/- 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI-I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. CONCLUSIONS: *These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.*





> Pramipexole for bipolar II depression: a placebo-controlled proof of concept study.
> Zarate CA Jr, Payne JL, Singh J, Quiroz JA, Luckenbaugh DA, Denicoff KD, Charney DS, Manji HK.
> 
> Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institute of Health, Department of Human and Health Services, Bethesda, Maryland, USA.
> ...





> Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression.
> Goldberg JF, Burdick KE, Endick CJ.
> 
> Department of Psychiatry, Weill Medical College of Cornell University, New York, NY, USA. [email protected]
> OBJECTIVE: Previous studies suggest that the dopamine agonist pramipexole may possess antidepressant properties. The authors conducted a preliminary randomized, placebo-controlled trial to determine the safety and antidepressant efficacy of pramipexole in treatment-resistant bipolar depression. METHOD: Twenty-two depressed outpatients with DSM-IV nonpsychotic bipolar disorder were randomly assigned to receive placebo or flexibly dosed pramipexole (mean maximum dose=1.7 mg/day, SD=1.3) added to existing mood stabilizers for 6 weeks. The primary outcome measure was response, defined as improvement in Hamilton Depression Rating Scale score of 50% or more over the baseline score; secondary analyses involved changes in Clinical Global Impression (CGI) severity scores. RESULTS: More patients given pramipexole (10 [83%] of 12) than patients given placebo (six [60%] of 10) completed the study. Eight (67%) of 12 patients taking pramipexole and two (20%) of 10 taking placebo had an improvement of at least 50% in their Hamilton depression scale scores. The mean percentage of improvement from baseline Hamilton depression scale scores was greater for patients taking pramipexole (48%) than for those taking placebo (21%). Mean improvements in CGI severity were also greater with pramipexole than placebo. No patients discontinued the study because of adverse events except for one patient who became hypomanic while taking pramipexole. CONCLUSIONS: *Pramipexole was a safe and effective antidepressant among patients with bipolar depression. Larger randomized, controlled trials are needed to affirm these initial observations.*


----------



## crayzyMed (Nov 2, 2006)

Part2



> Mechanism of synergistic action following co-treatment with pramipexole and fluoxetine or sertraline in the forced swimming test in rats.
> Rogóz Z, Skuza G.
> 
> Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. [email protected]
> The aim of the present study was to examine the effect of combined treatment of male Wistar rats with pramipexole and fluoxetine or sertraline in the forced swimming test. The obtained results showed that co-treatment with pramipexole (0.1 mg/kg) and fluoxetine (10 mg/kg) or sertraline (5 mg/kg) (in doses inactive per se) exhibited antidepressant-like activity in the forced swimming test. Sulpiride (a dopamine D(2/3) receptor antagonist) and WAY 100635 (a 5-HT(1A) receptor antagonist), either being ineffective in the forced swimming test, inhibited the antidepressant-like effect induced by co-administration of pramipexole and fluoxetine or sertraline. However, SCH 23390 (a dopamine D(1) receptor antagonist) only partly did not alter the effect of pramipexole given jointly with antidepressant drugs; on the other hand, S 33084 (a dopamine D(3) receptor antagonist) only partly decreased (in a statistically insignificant manner) that effect. Moreover, progesterone and BD 1047 (a sigma(1) receptor antagonist) counteracted the antidepressant-like effect induced by co-administration of pramipexole and sertraline (but not pramipexole and fluoxetine). In that test, active behavior did not reflect the increases in general activity, since combined administration of pramipexole and fluoxetine or sertraline failed to enhance the locomotor activity of rats. None of the tested drugs (SCH 23390, sulpiride, S 33084, WAY 100635, BD 1047 and progesterone) - alone or in combination with pramipexole and fluoxetine or sertraline - changed locomotor activity. *The results described in the present paper indicate that co-administration of pramipexole and fluoxetine or sertraline may induce a more pronounced antidepressive activity than does treatment with pramipexole alone, and that in addition to other mechanisms, dopamine D(2/3) and 5-HT(1A) receptors may contribute to the antidepressant-like activity of pramipexole and fluoxetine or sertraline in the forced swimming test in rats. Moreover, sigma(1) receptors may constitute one of the possible mechanisms by which co-administration of pramipexole and sertraline induces antidepressant-like activity in that test.*





> [The Role of Low-Dose Pramipexole in the Treatment of Treatment-Resistant Bipolar Depression: A Case Report.]
> [Article in Turkish]
> 
> Akdenız F, Aldemır E, Vahıp S. Despite a wide range of various drugs, a significant proportion of depressed bipolar patients fail to respond to the treatment strategies. Novel theraupetics for bipolar depression are needed. Preliminary studies suggest that pramipexole a dopaminergic agent that has been used in the treatment of Parkinson's disease and restless leg syndrome may have antidepressant properties in unipolar and bipolar depressed patients as well as neurotrophic properties. The optimal antidepressant daily dose of pramipexole is not known. It has been suggested to be used between 0.125 to 9.0 mg/day. In double blind placebo controlled bipolar depression treatment studies, the average daily dose of pramipexole was 1.7 mg. Manic switches have been reported with depressive subjects and with subjects without any mental disorders. We report two cases of treatment resistant bipolar depression. Despite different treatment strategies and treatment adherence, the patients did not give optimal response to the treatments and continue to experience depressive relapses. *They have been treated with low dose (0.5-0.75 mg/day) pramipexole augmentation successfully. The severity and the duration of the depressive episodes were decreased. No serious adverse event has been reported with pramipexole during the maintenance treatment.*
> ...





> Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease.
> Lemke MR, Brecht HM, Koester J, Reichmann H. Center of Psychiatry and Neurology, Rhine Clinic Bonn, Germany. [email protected]
> 
> Depression affects approximately 45% of all patients with Parkinson's disease, reduces quality of live independent of motor symptoms and seems to be underrated and undertreated. Pramipexole shows D(3)- versus D(2)-receptor preference at cortico-frontal dopamine receptors and neurotrophic effects which seem to relate to its antidepressant and anti-anhedonic properties in Parkinson's disease and bipolar depression found in controlled studies. In the present study, effects of pramipexole were investigated under routine clinical conditions. Anhedonia was measured in patients with Parkinson's disease (n=657) using the self-rated Snaith-Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated Short-Parkinson's-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all patients and in 79.7% of the depressed patients with Parkinson's disease. Mild depression was present in 47%, moderate to severe depression in 22% of the patients. At the end of the study period of 9 weeks on an average, the mean dosage of pramipexole was 1.0+/-0.6 mg/d (range 0.3 to 4.2). *Frequency of depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well as motor deficits were significantly reduced during treatment with pramipexole. Drop-outs due to adverse events occurred in 3.5%. Future studies should investigate specificity of anti-anhedonic and antidepressive properties of pramipexole.*
> ...





> Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study.
> Rektorová I, Rektor I, Bares M, Dostál V, Ehler E, Fanfrdlová Z, Fiedler J, Klajblová H, Kulist'ák P, Ressner P, Svátová J, Urbánek K, Velísková J. First Department of Neurology, Masaryk University, St Anne's Teaching Hospital, Brno, Czech Republic. [email protected]
> 
> An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. *Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.*
> ...





> Pramipexole has astrocyte-mediated neuroprotective effects against lactacystin toxicity.
> Imamura K, Takeshima T, Nakaso K, Ito S, Nakashima K. Department of Neurology, Institute of Neurological Sciences, Tottori University, Faculty of Medicine, Yonago, Tottori, Japan. [email protected]
> 
> Pramipexole, a dopamine D2/D3 receptor agonist used in the treatment of Parkinson's disease, has been reported to have neuroprotective potential. We investigated the effect of pramipexole against cell death induced by a proteasome inhibitor, lactacystin, using primary mecencephalic neuronal cultures and SH-SY5Y cells. In E14 rat primary mesencephalic cultures, the number of surviving tyrosine hydroxylase (TH)-positive neurons and microtubule associated protein 2 (MAP2)-positive neurons was decreased by exposure to 1-5 microM lactacystin in a dose-dependent manner. Pretreatment with 100 microM pramipexole rescued TH-positive neurons and MAP2-positive neurons from the toxicity of lactacystin. The protective effect of pramipexole was not selective for TH-positive dopaminergic neurons. However, the treatment with 100 microM pramipexole did not protect SH-SY5Y cells against lactacystin-induced cell toxicity and proteasome dysfunction. We hypothesized that the protective effect of pramipexole against the lactacystin-toxicity was not direct but a secondary effect mediated by astrocytes. Therefore, we investigated the efficacy of conditioned medium collected from mecencephalic astrocytes treated with pramipexole. The conditioned medium increased the viability of SH-SY5Y cells against the toxicity of lactacystin. Pramipexole increased the levels of brain derived neurotrophic factor (BDNF) in the conditioned medium of astrocyte cultures. These protective effects were not significantly inhibited by dopamine D2 or D3 receptor antagonists. *We demonstrated that pramipexole had the protective effect against lactacystin toxicity, mediated by a neurotrophic effect of astrocyte-produced factors including BDNF.*
> ...


----------



## crayzyMed (Nov 2, 2006)

Part3


> Pramipexole in psychiatry: a systematic review of the literature.
> Aiken CB. Department of Psychiatry, Wake Forest University School of Medicine, Winston-Salem, NC, USA. [email protected]
> 
> OBJECTIVE: To assess the risks and benefits of pramipexole in psychiatric populations. DATA SOURCES: A PubMed search was performed using the keywords pramipexole and ropinirole, which identified 500 articles. STUDY SELECTION: All clinical studies in psychiatric populations were included in the primary review (24 articles). Studies involving other populations were then reviewed to evaluate potential risks and benefits not identified in the psychiatric studies. DATA EXTRACTION: Effect sizes were calculated from controlled studies. Rates of intolerable side effects and manic switching were estimated by pooled analysis of controlled and uncontrolled studies. DATA SYNTHESIS: Pramipexole has a large effect size (0.6-1.1) in the treatment of both bipolar and unipolar depression with a low short-term rate of manic switching in bipolar patients (1% mania, 5% hypomania). The pooled discontinuation rate for all reasons was 9%. Pramipexole is neuroprotective and exerts beneficial effects on sleep architecture. Pramipexole is associated with 3 rare but serious side effects: sleep attacks, which have only occurred in Parkinson's disease; compulsive behaviors and pathologic gambling, which have occurred in Parkinson's disease and restless legs syndrome; and psychosis, which has occurred in both psychiatric and neurologic populations. CONCLUSIONS: *Pramipexole is an important therapeutic option for treatment-resistant bipolar and unipolar depression; further studies are warranted to evaluate its safety in psychiatric patients.*
> ...





> Sustained administration of pramipexole modifies the spontaneous firing of dopamine, norepinephrine, and serotonin neurons in the rat brain.
> Chernoloz O, El Mansari M, Blier P. Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada. [email protected]
> 
> Pramipexole (PPX) is a D(2)/D(3) receptor agonist that has been shown to be effective in the treatment of depression. Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems are known to be involved in the pathophysiology and treatment of depression. Due to reciprocal interactions between these neuronal systems, drugs selectively targeting one system-specific receptor can indirectly modify the firing activity of neurons that contribute to firing patterns in systems that operate via different neurotransmitters. It was thus hypothesized that PPX would alter the firing rate of DA, NE and 5-HT neurons. To test this hypothesis, electrophysiological experiments were carried out in anesthetized rats. Subcutaneously implanted osmotic minipumps delivered PPX at a dose of 1 mg/kg per day for 2 or 14 days. After a 2-day treatment with PPX the spontaneous neuronal firing of DA neurons was decreased by 40%, NE neuronal firing by 33% and the firing rate of 5-HT neurons remained unaltered. *After 14 days of PPX treatment, the firing rate of DA had recovered as well as that of NE, whereas the firing rate of 5-HT neurons was increased by 38%. It was also observed that sustained PPX administration produced desensitization of D(2)/D(3) and 5-HT(1A) cell body autoreceptors, as well as a decrease in sensitivity of alpha(2)-adrenergic cell body autoreceptors. These adaptive changes are implicated in long-term firing rate adaptations of DA, NE and 5-HT neurons after prolonged PPX administration. In conclusion, the therapeutic action of PPX in depression might be attributed to increased DA and 5-HT neurotransmission.*
> ...





> Synergistic effect of pramipexole and sertraline
> in the forced swimming test
> by
> Maj J, Rogoz Z.
> ...





> Pramipexole in treatment-resistant depression:
> An extended follow-up
> by
> Cassano P, Lattanzi L, Soldani F, Navari S,
> ...





> Potential antidepressant properties of pramipexole detected in locomotor and operant behavioral investigations in mice
> by
> Lehr E.
> Department of Pulmonary Research,
> ...


----------



## rawrguy (Mar 29, 2008)

Thx guys


----------



## rawrguy (Mar 29, 2008)

rocknroll714 said:


> Don't forget about increased appetite and weight gain as a side effect though.


ya man, that's definitely something to look out for. I've been exercising lately and trying to control my eating habits. I'll keep you guys updated on this.



> In reference to that first study crayzyMed posted, I wonder what 5.0 mg/d would be like? >


why don't you try for yourself to find out!  lol jk i know you wouldn't want to. honestly anyone that would go on that high of a dose for 4-7 weeks i would consider either brave or insane D:


----------



## rawrguy (Mar 29, 2008)

Thanks a lot for the advice, but I'm sure I won't be getting off of it if this works for me. So far I haven't had those side effects.


----------



## rawrguy (Mar 29, 2008)

Just checked my Liebowitz SA scale for the first time. I have a 22 lol.


----------



## Medline (Sep 23, 2008)

rawrboy64 said:


> Just checked my Liebowitz SA scale for the first time. I have a 22 lol.


That would mean no SAD at all.


----------



## rawrguy (Mar 29, 2008)

Yeah


----------



## crayzyMed (Nov 2, 2006)

Not suprising since dopamine is highly implicated in social anxiety.


----------



## zenlee (Nov 26, 2010)

I am planning to start taking 
Moclobemide (maoi ) 3 x 150 mg daily.
Pramipexol 3 x 0,25 mg daily.
what do you think about interaction betwen these two medication?


----------



## Canadian4Life (Sep 27, 2010)

Glad pramipexole is working for you! It is one drug I can vouch for. I find the lower the dose (1mg a day or less) can help depression and anhedonia and doses of 4mg a day or more can make this worse. If the drug is working for you then keep at it..you don't need to see studies saying that it's effective....you already know. I have been on alot of drugs and did alot of research. Going by studies may help and it also could lead you astray. All the studies I read on the drugs I took and the experience I Actually had was sometimes the same and most time very different. Plain and simple..a study can show you prozac has significant benefits in treating depression and go on it to fing out it makes you worse and more depressed than you've ever been. If the drug works for you don't question it. Other peoples experiences and comments on a certain drug can be Very misleading also. You might read someones experience with an ssri,benzo or stimulant and read all the horror it caused them, then not try the drug or think "it's bad" when that exact drug could be what helps you out majorly. Everyone's brain is wired differently..to a degree of course and what works for one mightn't work for you and vice versa. Stick with what works for you and don't listen to others telling you a drug is useless until you try it yourself. But anyways yes pramipexole can be a great antidepressant in low doses and is neuroprotective as well. One of the best drugs I've taken alongside my ritalin and clonazepam.


----------



## Naked Ape (Apr 5, 2010)

rawrguy said:


> Lately I have been on 3.0mg of Pramipexole, a dopamine agonist used to treat Parkinson's Disease, and I've gotta say it's awesome. My social inhibitions are waay lower, I would even say they are close to gone. So far I have been on Pramipexole for 3 months on 3 different doses.





Guide 4 Dummies said:


> Just be careful..
> 
> Pramipexole fixed my SAD, but in the process it made me long-term anhedonic/apathetic. The withdrawal is so brutal and so prolonged it surpassed Alprazolam cold-turkey. Some people compare it to Tramadol withdrawal except that Prami withdrawal lasts forever and does not decrease in severity.
> 
> I relapsed 3 times already, I've considered being on Prami for the rest of my life.


Hi what happend with your cure based on Pramipexole?

Does it still work? Is it a magic tolerance free medication?


----------



## crayzyMed (Nov 2, 2006)

Naked Ape said:


> Hi what happend with your cure based on Pramipexole?
> 
> Does it still works? Is it magic tolerance free medication?


Caused severe apathy in bot, id skip this **** and go for amphetamine.


----------



## RoseMaria (Apr 18, 2021)

rawrguy said:


> Lately I have been on 3.0mg of Pramipexole, a dopamine agonist used to treat Parkinson's Disease, and I've gotta say it's awesome. My social inhibitions are waay lower, I would even say they are close to gone. So far I have been on Pramipexole for 3 months on 3 different doses. The main thing with pramipexole is when you first start the medication, your dopamine shoots straight down, especially if you go straight to higher doses like I did. Side effects during the first four weeks include:
> 
> Nausea
> panic attacks whenever you go out
> ...


Hey how long did it take for this medication to start making you feel better?


----------



## ChopSuey (Nov 5, 2012)

rawrguy said:


> Lately I have been on 3.0mg of Pramipexole, a dopamine agonist used to treat Parkinson's Disease, and I've gotta say it's awesome. My social inhibitions are waay lower, I would even say they are close to gone. So far I have been on Pramipexole for 3 months on 3 different doses. The main thing with pramipexole is when you first start the medication, your dopamine shoots straight down, especially if you go straight to higher doses like I did. Side effects during the first four weeks include:
> 
> Nausea
> panic attacks whenever you go out
> ...


As expected from a notable dopamine increase. Dopamine is perhaps the most important neurotransmitters when it comes to social anxiety, yet we barely have any medications available that exerts such a function, and the few that do exist are limited for treating other kinds of medical disorders.. Insanity. Medicine companies and dem doctors need to wake up in that regard.

But in the case of Pramipexole and its mechanism, the euphoric effects will sadly wear off with time. Enjoyable while it lasts. And sadly the euphoric effects will eventually come with a downside; you'll feel like a lazy bag of potatoes with low motivation when the effects have settled and dopamine has normalized.


----------

