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Table of Contents

1. Chemistry and Pharmacology

   • Chemical Composition
   • Pharmacological Actions
   • Receptor Interactions
   • Indirect Agonism
   • Pharmacokinetics

2. Dosage and Bioavailability

   • Bioavailability
   • Dosage Categories

3. Physical, Auditory, Cognitive, and Visual Effects

   • Physical Effects
   • Auditory Effects
   • Cognitive Effects
   • Visual Effects
   • Combination Effects

4. Toxicity and Harm Potential

   • Toxicity
   • Dependence and Abuse Potential
   • Overdose
   • Dangerous Interactions
   • Legal Status

5. FAQ (Frequently Asked Questions)

Exploring Mirtazapine: An Atypical Antidepressant

Introduction to Mirtazapine

Mirtazapine, commonly known under the trade name Remeron, belongs to the piperazinoazepine class of antidepressants. Despite its primary function as an antidepressant, reports indicate that at higher doses, it exhibits atypical psychedelic and sedative properties. Classified as a noradrenergic and specific serotonergic antidepressant (NaSSA), mirtazapine's development originated in the Netherlands and it was introduced to the United States pharmaceutical market in 1996. Since the expiration of its patent in 2004, generic versions have become widely available.

Medical Applications

Primarily prescribed for major depressive disorder and various mood disorders, mirtazapine also finds off-label use in treating conditions such as generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, low appetite, insomnia, nausea/vomiting, itching, and headaches/migraines.

Psychedelic and Sedative Effects

At doses surpassing the recommended prescription levels, mirtazapine users report a unique blend of psychedelic and sedative effects. These effects encompass sedation, mild to moderate open and closed-eye visuals, enhanced conceptual thinking, and euphoria. However, there's a peculiar aspect regarding its sedative properties. Anecdotal evidence and some studies suggest that its sedative effects diminish as the dosage increases, with lower doses inducing greater sedation than higher doses. One hypothesis posits minor stimulant effects that may counterbalance its sedative properties, leading to this paradoxical effect.

Health Risks and Recommendations

The toxicity and health risks associated with recreational mirtazapine use remain largely unknown. Therefore, individuals considering its recreational use are strongly advised to adhere to harm reduction practices to mitigate potential adverse effects and risks associated with its consumption.

Exploring Mirtazapine: Chemistry and Pharmacology

Chemical Composition

Mirtazapine is a synthetic tetrahedral molecule belonging to the piperazino-azepine and phenethylamine group of compounds. Structurally, it comprises a fusion of pyridine, benzene, azepine, and piperazine rings, characteristic of its tetracyclic antidepressant nature. It is notably the 6-aza analog of mianserin, a compound with similar pharmacological functions.

Pharmacological Actions

Mirtazapine exerts its pharmacological effects by enhancing central adrenergic and serotonergic transmission. This enhancement is attributed to its actions as an antagonist at central presynaptic alpha 2 adrenergic inhibitory autoreceptors and heteroreceptors. Additionally, mirtazapine serves as a potent antagonist of 5-hydroxytryptamine type 2 (5-HT2), 5-HT3, and histamine 1 (H1) receptors, and a moderate antagonist of peripheral alpha 1 adrenergic and muscarinic receptors.

Receptor Interactions

Mirtazapine acts as an antagonist/inverse agonist on various receptors including:

• 5-HT2A receptor
• 5-HT2B receptor
• 5-HT2C receptor
• 5-HT3 receptor
• 5-HT7 receptor
• α1-adrenergic receptor
• α2A-adrenergic receptor
• α2B-adrenergic receptor
• α2C-adrenergic receptor
• H1 receptor
• mACH receptors

While mirtazapine exhibits affinity for the 5-HT2A receptor, its antagonist action makes it unlikely to be responsible for its psychedelic and deliriant effects.

Indirect Agonism

Mirtazapine indirectly agonizes the κ3 opioid receptor, contributing to pain relief and augmenting the sedative and hallucinogenic effects. This mechanism may also underlie mirtazapine's withdrawal/discontinuation effects and its promotion of diuresis and increased food intake, often leading to weight gain.

Pharmacokinetics

Mirtazapine demonstrates an oral bioavailability of approximately 50% and is primarily bound to plasma proteins, accounting for around 85%. Metabolism primarily occurs in the liver via demethylation and hydroxylation facilitated by cytochrome P450 enzymes, namely CYP1A2, CYP2D6, and CYP3A4. One major metabolite is desmethylmirtazapine. The elimination half-life ranges from 20 to 40 hours, with conjugation in the kidney facilitating urinary excretion (75%) and a minor portion excreted in feces (15%).

Subjective Effects and Safety Considerations

While mirtazapine predominantly induces psychedelic effects, the hallucinations it produces often exhibit deliriant-like characteristics, being remarkably realistic and lacking condensed visual geometry. High-dose mirtazapine experiences typically result in a mental state devoid of insight, introspection, problem-solving, or creativity enhancement, diminishing its therapeutic potential as a hallucinogen.

Disclaimer: The effects described are based on anecdotal user reports and PsychonautWiki contributors' analyses, thus should be approached with caution. Higher doses increase the likelihood of adverse effects, including addiction, severe injury, or death.

Understanding Mirtazapine Dosage and Bioavailability

Bioavailability

Mirtazapine exhibits a bioavailability of approximately 50%, meaning about half of the administered dose reaches systemic circulation unchanged. This factor plays a crucial role in determining the effective dosage and potential effects experienced by users.

Dosage Categories

Threshold

• Threshold Dose: 3.5 mg
  • At this dose, minimal effects may be noticeable, serving as a starting point for individuals sensitive to mirtazapine's effects.

Light

• Light Dose Range: 70 - 130 mg
  • Within this range, users may experience mild to moderate effects, including subtle alterations in mood and perception.

Common

• Common Dose Range: 130 - 190 mg
  • Falling within this range, users can expect more pronounced effects, potentially including enhanced mood, altered perception, and increased sedation.

Strong

• Strong Dose Range: 190 - 250 mg
  • At these doses, users may encounter intense effects, characterized by significant alterations in mood and perception, along with heightened sedation.

Heavy

• Heavy Dose: 250 mg and above
  • Doses exceeding 250 mg are considered heavy and may induce profound and potentially overwhelming effects, including extreme sedation and intense alterations in mood and perception.

Understanding these dosage categories can help individuals gauge their mirtazapine intake more effectively, taking into account both their desired outcomes and potential risks associated with higher doses.

Understanding the Physical, Auditory, Cognitive, and Visual Effects of Mirtazapine

Physical Effects

• Sedation: Mirtazapine induces extreme sedation, often leading to a profoundly lethargic state where users feel overwhelmingly tired and may even pass out.
• Spontaneous Bodily Sensations: Users may experience a pleasurable tingling sensation throughout the body, accompanied by mild throbbing or aching sensations.
• Tactile Hallucination: Unique tactile hallucinations manifest as structured vibrations and pulsations across the skin, extending outward from their center.
• Changes in Felt Gravity
• Motor Control Loss: Engaging in physical activities may result in a distinct loss of motor control, accompanied by a sensation akin to walking on a trampoline.
• Appetite Enhancement: Mirtazapine induces intense appetite enhancement, similar in strength to the "munchies" experienced with cannabis.
• Constipation
• Dizziness
• Dry Mouth
• Bronchodilation: Difficulty swallowing may occur, particularly during the onset phase, similar to anticholinergic drugs like diphenhydramine.
• Muscle Relaxation
• Restless Legs
• Nausea Suppression

Auditory Effects

• Auditory Distortion
• Auditory Hallucination
• Auditory Enhancement

Cognitive Effects

• Thought Deceleration
• Analysis Suppression
• Cognitive Euphoria or Cognitive Dysphoria: Reports vary, with some users experiencing mild euphoria and others feeling neutral or dysphoric due to pronounced side effects.
• Dream Potentiation
• Conceptual Thinking
• Amnesia
• Immersion Enhancement
• Time Distortion
• Increased Music Appreciation
• Irritability
• Emotion Suppression: Mirtazapine dulls emotions, making it difficult to express them.
• Anxiety Suppression: This effect is stronger and more rapidly acting than that of SSRIs.

Visual Effects

• Distortions
• Visual Acuity Suppression
• Tracers
• Drifting (Melting, Flowing, Breathing, and Morphing)
• Color Tinting
• Color Shifting
• Symmetrical Texture Repetition
• Visual Haze
• Geometry: High doses induce visual geometry comparable to LSD or psilocin, characterized by intricate complexity, abstract style, and structured organization.
• Hallucinatory States: External and internal hallucinations may occur, resembling experiences found in deliriants but usually manifesting at high doses.

Combination Effects

• Cannabis: Combined with cannabis, mirtazapine's euphoric and visual effects are potentiated.
• Psychedelics: Mirtazapine's action as a 5-HT2A antagonist can help reduce the intensity or "abort" a bad trip when combined with psychedelics.

Toxicity and Harm Potential

Mirtazapine has low toxicity relative to dose and is not known to cause brain damage. However, caution is advised regarding overdose, as it can lead to adverse effects. Dependence and abuse potential are minimal, and overdose is relatively safe compared to other antidepressants.

Legal Status

Mirtazapine is legally approved for medical use worldwide but typically requires a prescription for purchase. In some countries, possession without a prescription may be illegal.

FAQ (Frequently Asked Questions)

Q: What is mirtazapine?

A: Mirtazapine is an antidepressant medication belonging to the piperazinoazepine class, commonly prescribed for the treatment of major depressive disorder and various mood disorders.

Q: What are the common dosage ranges for mirtazapine?

A: The common dosage ranges for mirtazapine are as follows:

• Threshold: 3.5 mg
• Light: 70 - 130 mg
• Common: 130 - 190 mg
• Strong: 190 - 250 mg
• Heavy: 250 mg and above

Q: What are the physical effects of mirtazapine?

A: Physical effects may include sedation, spontaneous bodily sensations, tactile hallucinations, changes in felt gravity, motor control loss, appetite enhancement, constipation, dizziness, dry mouth, bronchodilation, muscle relaxation, restless legs, and nausea suppression.

Q: Are there any auditory effects associated with mirtazapine use?

A: Yes, auditory effects may include distortion, hallucination, and enhancement.

Q: Can mirtazapine cause cognitive effects?

A: Yes, cognitive effects may include thought deceleration, analysis suppression, euphoria or dysphoria, dream potentiation, conceptual thinking, amnesia, immersion enhancement, time distortion, increased music appreciation, irritability, emotion suppression, and anxiety suppression.

Q: What visual effects can be experienced with mirtazapine use?

A: Visual effects may include distortions, visual acuity suppression, tracers, drifting, color effects, symmetrical texture repetition, visual haze, and geometric patterns.

Q: Is mirtazapine safe to use?

A: Mirtazapine is generally considered safe when used as prescribed. However, caution should be exercised regarding potential overdose and dangerous interactions with other substances.

Q: What is the legal status of mirtazapine?

A: Mirtazapine is legally approved for medical use in many countries but typically requires a prescription for purchase. Possession without a prescription may be illegal in some jurisdictions.