Mirtazapine

Mirtazapine
The skeletal formula of mirtazapine
Chemical Nomenclature
Common names	Avanza, Axit, Mirtaz, Mirtazon, Remeron, Zispin
Substitutive name	Mirtazapine
Systematic name	(±)-2-methyl-1,2,3,4,10,14b-hexahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepine
Class Membership
Psychoactive class	Antidepressant / deliriant / psychedelic
Chemical class	Tetracyclic antidepressant
Routes of Administration
Oral Dosage WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy. Threshold 20 - 50 mg Light 50 - 100 mg Common 100 - 150 mg Strong 150 - 200 mg Heavy 200 mg + Duration Onset 15 - 30 min Peak 90 - 180 min Offset 2 - 6 hours After effects up to 12 hours

Mirtazapine (Remeron, Avanza, or Zispin) is a noradrenergic and specific serotonergic tetracyclic antidepressant with hallucinogenic properties. It was originally introduced by Organon International in the United States in 1990. It is used primarily in the treatment of Major Depressive Disorder and other mood disorders.^[1][2] However, it has also been found useful in alleviating the following conditions and may be prescribed off-label for the treatment of Generalized Anxiety Disorder,^[3][4] Social Anxiety Disorder,^[5][6] Obsessive-Compulsive Disorder,^[7][8] Panic Disorder,^[9][10][11] Post-traumatic Stress Disorder,^[12] low appetite,^[13][14][15] insomnia,^[16][17] nausea/vomiting,^[18][19][20] itching,^[21][22]and headaches and migraines.^[23][24][25] At high dosages, however, Mirtazapine acts as an extremely sedating A-typical psychedelic-deliriant.

It is broadly classified as a centrally acting α2-adrenergic receptor antagonist. Its patent expired in 2004 and hence generic versions are now available.^[26]

Mirtazapine a tertrahedric molecule of the piperazino-azepine group of compounds. It is comprised of a fusion of pyradine, benzene, azepine, and pyrazine rings. Mirtazapine is a tetracyclic antidepressants, named so because of their four-ring structure. Mirtazapine is the 6-aza analogue of mianserin, which is pharmacologically similar in function.

Mirtazapine acts as an antagonist/inverse agonist upon the following receptors:^[27][28]

• 5-HT_2A receptor^[29]
• 5-HT_2B receptor^[30]
• 5-HT_2C receptor ^[29]
• 5-HT₃ receptor
• 5-HT₇ receptor
• α₁-adrenergic receptor^[31]
• α_2A-adrenergic receptor^[32]
• α_2B-adrenergic receptor^[33]
• α_2C-adrenergic receptor^[34]
• H₁ receptor^[35]
• mACH receptors^[36]

Its action upon the 5-HT_2A receptor and the H₁ receptor may lead to its mix of psychedelic and deliriant effects.

Mirtazapine has also been observed to indirectly agonise the following GCPR in humans:

• Opioid receptor κ₃^[37]

Mirtazapine has also been found to modulate the κ₃ opioid receptor, supporting the claim that mirtazapine causes pain relief^[38] and adds to the sedative and hallucinogenic effects of mirtazapine^[39][40]. This even may explain mirtazapine's withdrawal/discontinuation effects as well as its promotion of diurensis and a possible increase in food intake (usually resulting in weight gain).

It should be noted that although some of these effects are observed in those who take mirtazapine recreationally (or one off dosing) most neurophysiological effects are observed in those with on-going use (15, 30 and 45mg daily prescribed for depression, etc) due to a maintained level of mirtazapine in the body.

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.

Physical effects

• Spontaneous tactile sensations - The "body high" of mirtazapine can be described as a pleasurable, warm, soft and all-encompassing tingling sensation. This maintains a consistent presence that steadily rises with the onset and hits its limit once the peak has been reached and is not capable of becoming anything but mildly euphoric even at high dosages. This is accompanied by strange but mild throbbing or aching sensations.
• Sedation - In terms of energy level alterations, mirtazapine is extremely sedating and often results in an overwhelmingly lethargic state. This causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness. It is a state which often leaves people feeling extremely lethargic and tired the following day.
• Tactile hallucinations - Unique tactile hallucinations are commonly felt within this substance. These can be described as bizarrely structured vibrations and pulsations that spontaneously manifest themselves across the skin.
• Motor control loss - If physical activities such as walking are forcibly engaged in, a distinct but not completely incapacitating loss of motor control is noticed as well as the consistent feeling that you are walking on top of a trampoline and not a normal solid floor.
• Appetite enhancement - The above components are also accompanied by an intense appetite enhancement that is identical in strength to “the munchies” experienced with marijuana.
• Constipation
• Dizziness

Cognitive effects

The mental processes, thought patterns and general head space experienced during a high dose mirtazapine trip is one that is completely devoid of insight. There is seemingly no introspection, personal problem solving or creative insight to be found with this substance whatsoever and it’s because of this that mirtazapine holds absolutely no therapeutic potential when used as a hallucinogen.

These effects generally include:

• Thought deceleration
• Information processing suppression
• Amnesia

Visual effects

Distortions

• Tracers - This effect is very common and is more capable of manifesting itself at level 4 than most (if not all) traditional psychedelics.

Geometry

In terms of complexity, the visual geometry found within high dose mirtazapine trips can be said to be completely on par with that of LSD or psilocin. It can be comprehensively described as intricate in complexity, abstract in style, structured in organization, equally organic and synthetic in style, dimly lit in lighting, monotone is scheme, glossy in shading, equal in sharp and soft edges, large in size, fast in speed, smooth in motion, equal in rounded and angular corners, non-immersive in depth and consistent in intensity.

At higher dosages, Level 8A and Level 8B are not present simply because the sedating effects are too overwhelming to allow people to remain conscious at such a high level. Many users report an almost menacing feeling, following a sinister and ominous style with a colour scheme that generally consists of greys and blues.

Hallucinatory states

• External hallucinations (Autonomous entities, Settings, sceneries, and landscapes, Perspective alterations and Scenarios and plots) - This effect is very similar to the same experience found within deliriants but does not manifest itself consistently and usually happens only at high dosages. It can be comprehensively described through its variations as delirious in believability, autonomous in controllability and solid in style.
• Internal hallucinations (autonomous entities; settings, sceneries, and landscapes; perspective alterations and scenarios and plots) - The internal hallucinations which mirtazapine induces are generally only present as spontaneous breakthroughs at extremely high dosages as one is falling asleep. This effect's variations are delirious in believability, interactive in style, new experiences in content, autonomous in controllability and solid in appearance. The most common way in which they manifest themselves are through hypnagogic scenarios which the user may experience as they are drifting off to sleep. These are short and fleeting but frequent and completely believable and convincing as they happen. In terms of the theme they often take the form of bizarre and extremely nonsensical plots. These can also be observed in hypnopompic states (when one is waking from sleep).

Auditory effects

• Distortions
• Hallucinations

Classification

Although mirtazapine exhibits almost exclusively psychedelic effects, the hallucinations that accompany it do have distinctively deliriant-like effects. For example, they are often delirious in their believability and rarely comprised of condensed visual geometry. Instead they tend to be solid and extremely realistic in appearance.

This can be explained by the way in which mirtazapine fits into both the 5HT receptor system found within all traditional psychedelics as well as the H1 histamine receptor responsible for the delirious effects found with drugs such as DPH and datura. It is because of these subjective and pharmacological effects that PsychonautWiki classifies mirtazapine as a psychedelic deliriant and not one or the other.

This document, provided with prescription mirtazapine, contains detailed information regrading its toxicity and harm potential.

Mirtazapine is not known to cause brain damage, and has extremely low toxicity relative to dose. Similar to other psychedelic drugs, there are relatively few physical side effects associated with mirtazapine exposure. Various studies have shown that in reasonable doses in a careful context, it presents no negative cognitive, psychiatric or toxic physical consequences of any sort.

Lethal dosage

Although the exact toxic dose is unknown, mirtazapine is considered by the medical literature to be relatively safe in the event of an overdose.^[41] There are no significant cardiovascular adverse effects at 7 to 22 times the maximum recommended dose which is 45mg.^[42] The LD50 is 600-720mg/kg (oral, mice) and 320-490mg/kg (oral, rat) which extrapolates to something roughly between 2.9g - 3.6g for a 60kg human. This is 13 times or more the recreational dosage of roughly 210mg.

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

Mirtazapine is not habit-forming when used as a hallucinogen and the desire to use it can actually decrease with use. It is most often self-regulating.

Tolerance to the effects of mirtazapine are built almost immediately after ingestion. After that, it takes about 3 days for the tolerance to be reduced to half and 7 days to be back at baseline (in the absence of further consumption). Mirtazapine presents cross-tolerance with all psychedelics, meaning that after the consumption of mirtazapine all psychedelics will have a reduced effect.

This legality section is a stub. As such, it likely contains incomplete or wrong information. You can help by expanding it.

Mirtazapine is legally approved for medical purposes worldwide. However, it is illegal to sell and possess in most countries without a prescription.

Anecdotal reports which describe this compound within our experience index include:

• Experience:120mg - Unexpected 'trip', insane CEVs

• Responsible use
• Psychedelics
• Deliriants

• Mirtazapine (Wikipedia)
• Mirtazapine (Erowid)
• Mirtazapine (Drugs.com)
• Mirtazapine (Disregard Everything I Say)
• Mirtazapine experiences (Erowid)

1. ↑ Mirtazapine: clinical overview. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/10446735
2. ↑ Review of the use of mirtazapine in the treatment of depression | http://informahealthcare.com/doi/abs/10.1517/14656566.2011.585459
3. ↑ A Review of the Pharmacological and Clinical Profile of Mirtazapine | http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2001.tb00198.x/abstract
4. ↑ Mirtazapine in Major Depression With Comorbid Generalized Anxiety Disorder | http://dx.doi.org/10.4088%2FJCP.v60n0705
5. ↑ http://link.springer.com/article/10.2165%2F00023210-200923050-00006
6. ↑ Mirtazapine Treatment of Social Phobia in Women: A Randomized, Double-Blind, Placebo-Controlled Study | http://journals.lww.com/psychopharmacology/pages/articleviewer.aspx?year=2005&issue=12000&article=00015&type=abstract
7. ↑ http://link.springer.com/article/10.2165%2F00023210-200923050-00006
8. ↑ Mirtazapine Treatment of Obsessive-Compulsive Disorder | http://journals.lww.com/psychopharmacology/Citation/2001/10000/Mirtazapine_Treatment_of_Obsessive_Compulsive.16.aspx
9. ↑ http://link.springer.com/article/10.2165%2F00023210-200923050-00006
10. ↑ Clinical Experience with Mirtazapine in the Treatment of Panic Disorder | http://www.crossref.org/iPage?doi=10.3109%2F10401239909147053
11. ↑ Mirtazapine in the Treatment of Panic Disorder | http://archpsyc.jamanetwork.com/article.aspx?articleid=1151071
12. ↑ http://link.springer.com/article/10.2165%2F00023210-200923050-00006
13. ↑ http://www.ncbi.nlm.nih.gov/pubmed/12647431
14. ↑ Appetite stimulants in cystic fibrosis: a systematic review | http://onlinelibrary.wiley.com/doi/10.1111/j.1365-277X.2007.00824.x/abstract
15. ↑ Management of symptons associated with advanced cancer: olanzapine and mirtazapine | http://informahealthcare.com/doi/abs/10.1586/14737140.2.4.365
16. ↑ http://www.ncbi.nlm.nih.gov/pubmed/9917581
17. ↑ Insomnia in Patients with Depression | http://link.springer.com/article/10.2165%2F00023210-200923040-00004
18. ↑ Tolerability and safety aspects of mirtazapine | http://onlinelibrary.wiley.com/doi/10.1002/hup.388/abstract
19. ↑ Mirtazapine Relieves Post-Electroconvulsive Therapy Headaches and Nausea: A Case Series and Review of the Literature | http://journals.lww.com/ectjournal/pages/articleviewer.aspx?year=2011&issue=06000&article=00016&type=abstract
20. ↑ Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects | http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2354.2006.00760.x/abstract
21. ↑ Itch: scratching more than the surface | http://qjmed.oxfordjournals.org/content/96/1/7
22. ↑ Itch in systemic disease: therapeutic options | http://onlinelibrary.wiley.com/doi/10.1111/j.1529-8019.2005.00036.x/abstract
23. ↑ Mirtazapine Relieves Post-Electroconvulsive Therapy Headaches and Nausea: A Case Series and Review of the Literature | http://journals.lww.com/ectjournal/pages/articleviewer.aspx?year=2011&issue=06000&article=00016&type=abstract
24. ↑ Therapy of primary headaches: the role of antidepressants | http://link.springer.com/article/10.1007%2Fs10072-004-0280-x
25. ↑ [Effects of mirtazapine in patients with chronic tension-type headache. Literature review]. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17073214
26. ↑ Schatzberg, AF; Cole, JO; DeBattista, C. "3". Manual of Clinical Psychopharmacology (7th ed.). Arlington, VA: American Psychiatric Publishing.
27. ↑ Discovery of New Tetracyclic Tetrahydrofuran Derivatives as Potential Broad-Spectrum Psychotropic Agents | http://pubs.acs.org/doi/abs/10.1021/jm049632c
28. ↑ Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, org 3770 and its enantiomers (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/0028390888901499
29. ↑ ^{29.0 29.1} Fernández J, Alonso JM, Andrés JI, Cid JM, Díaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA. (2005) Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J. Med. Chem., 48 (6): 1709-12. [PMID:15771415]
30. ↑ The pharmacologic profile of mirtazapine. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8636062
31. ↑ Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (in English) (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
32. ↑ https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05345-3
33. ↑ Kennis LE, Bischoff FP, Mertens CJ, Love CJ, Van den Keybus FA, Pieters S, Braeken M, Megens AA, Leysen JE. (2000) New 2-substituted 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine having highly active and potent central alpha 2-antagonistic activity as potential antidepressants. Bioorg. Med. Chem. Lett., 10 (1): 71-4. [PMID:10636247]
34. ↑ https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05345-3
35. ↑ Synthesis and Pharmacological Testing of 1,2,3,4,10,14b-Hexahydro-6-methoxy-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin and Its Enantiomers in Comparison with the Two Antidepressants Mianserin and Mirtazapine | http://pubs.acs.org/doi/abs/10.1021/jm010566d
36. ↑ Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (in English) (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8
37. ↑ Schreiber, S., Rigai, T., Katz, Y., & Pick, C. G. (2002). The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms. Brain research bulletin, 58(6), 601-605.
38. ↑ Dapoigny M, Abitbol JL, Fraitag B. (1995) Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome. A multicenter dose-response study. Dig Dis Sci, 40: 2244-2249. [PMID:7587797]
39. ↑ Pande AC, Pyke RE, Greiner M, Wideman GL, Benjamin R, Pierce MW. (1996) Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain. Clin Neuropharmacol, 19: 451-456. [PMID:8889289]
40. ↑ Rimoy GH, Wright DM, Bhaskar NK, Rubin PC. (1994) The cardiovascular and central nervous system effects in the human of U-62066E. A selective opioid receptor agonist. Eur J Clin Pharmacol, 46: 203-207. [PMID:8070500]
41. ↑ Taylor, D; Paton, C; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry (in English). West Sussex: Wiley-Blackwell. ISBN 978-0-470-97948-8.
42. ↑ Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression | http://www.jad-journal.com/article/S0165-0327(98)00224-9/abstract