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Table of Contents

1. Chemistry and Pharmacology

   • Molecular Structure
   • Pharmacological Insights
   • Receptor Interactions
   • Indirect Agonism and Modulation
   • Pharmacokinetics

2. Dosage and Bioavailability

   • Understanding Bioavailability
   • Exploring Dosage Ranges

3. Physical and Cognitive Effects

   • Physical Effects
   • Cognitive Effects
   • Visual Effects
   • Exploring Hallucinatory States

4. FAQ (Frequently Asked Questions)

   • Is mirtazapine habit-forming?
   • What are the dangers of mirtazapine overdose?
   • Can mirtazapine interact with other medications?
   • What is the legal status of mirtazapine worldwide?

Exploring Mirtazapine: From Antidepressant to Psychedelic Sedative

Understanding Mirtazapine

Mirtazapine, known by its trade name Remeron and others, belongs to the piperazinoazepine class of antidepressant substances. While primarily recognized for its antidepressant properties, at higher doses, it exhibits atypical psychedelic and sedative effects. Classified as a noradrenergic and specific serotonergic antidepressant (NaSSA), its therapeutic applications extend beyond depression into various mood disorders.

Development and Usage

Developed in the Netherlands, mirtazapine made its debut in the United States pharmaceutical market in 1996. Following the expiration of its patent in 2004, generic versions became readily accessible. Its primary medical use lies in the treatment of major depressive disorder and assorted mood disorders. Additionally, it finds off-label applications in 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 and migraines.

Psychedelic and Sedative Effects

Beyond its prescribed dosage, mirtazapine unveils a unique blend of psychedelic and sedative impacts. Users report experiencing sedation alongside mild to moderate open and closed-eye visuals, conceptual thinking, and euphoria. Notably, there's a paradoxical relationship between dosage and sedation. Anecdotal accounts and limited studies suggest that sedation decreases with increasing doses, with 7.5mg being more sedating than 15mg. One proposed theory posits minor stimulant effects that overpower its sedative properties.

Considerations for Recreational Use

The recreational use of mirtazapine raises concerns about toxicity and health risks, yet comprehensive data on these aspects remain elusive. As a precautionary measure, it is strongly recommended to employ harm reduction practices when using this substance.

Deciphering the Chemistry of Mirtazapine

Molecular Structure

Mirtazapine, a synthetic compound, belongs to the piperazino-azepine and phenethylamine group. Structurally, it comprises a fusion of pyridine, benzene, azepine, and piperazine rings, making it a tetrahedral antidepressant due to its four-ring structure. Notably, it is the 6-aza analog of mianserin, sharing pharmacological similarities.

Pharmacological Insights

Mirtazapine exerts its effects by enhancing central adrenergic and serotonergic transmission. This mechanism involves its action as an antagonist at central presynaptic alpha 2 adrenergic inhibitory autoreceptors and heteroreceptors. Additionally, it acts 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

The pharmacological activity of mirtazapine involves its interaction with various receptors, including:

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

While it exhibits affinity for the 5-HT2A receptor, it functions as an antagonist, suggesting that this mechanism may not be responsible for its psychedelic effects.

Indirect Agonism and Modulation

Mirtazapine indirectly agonizes the κ3 opioid receptor, contributing to pain relief and enhancing sedative and hallucinogenic effects. This modulation may also explain withdrawal symptoms, diuresis promotion, and increased food intake associated with mirtazapine use.

Pharmacokinetics

Mirtazapine demonstrates an oral bioavailability of approximately 50% and exhibits high plasma protein binding (around 85%). Metabolism primarily occurs in the liver through demethylation and hydroxylation mediated by cytochrome P450 enzymes (CYP1A2, CYP2D6, CYP3A4). One major metabolite is desmethylmirtazapine. The drug's elimination half-life ranges from 20 to 40 hours, with renal excretion (75%) and fecal elimination (15%).

Exploring Subjective Effects and Considerations

Psychedelic Characteristics

Despite its primarily psychedelic effects, mirtazapine-induced hallucinations often exhibit deliriant-like qualities. These hallucinations are characterized by their realism and believability, lacking condensed visual geometry typical of other psychedelics. Moreover, high-dose experiences are marked by a lack of introspection, problem-solving, or creativity enhancement, suggesting limited therapeutic potential when used as a hallucinogen.

Cautionary Notes

It's essential to approach mirtazapine use with caution, especially in recreational settings. Effects may vary unpredictably, with higher doses posing increased risks of adverse outcomes, including addiction, severe injury, or even death. Thus, informed decision-making and adherence to safety guidelines are paramount.

Navigating Dosage and Bioavailability of Mirtazapine

Understanding Bioavailability

Mirtazapine exhibits a bioavailability of approximately 50%, indicating the proportion of the drug that enters circulation when administered orally. This parameter significantly influences dosage considerations and overall drug efficacy.

Exploring Dosage Ranges

• Threshold: The minimum dosage required to elicit noticeable effects is around 3.5 mg.

• Light: Users typically experience mild effects within the range of 70 to 130 mg.

• Common: Dosages between 130 and 190 mg are associated with more pronounced effects, representing a standard dosage range for many users.

• Strong: Intensity increases within the range of 190 to 250 mg, leading to stronger effects.

• Heavy: Dosages exceeding 250 mg are considered heavy and may lead to particularly intense experiences.

Understanding these dosage categories is crucial for safe and informed use of mirtazapine.

Analyzing Physical and Cognitive Effects of Mirtazapine

Physical Effects

• Sedation: Mirtazapine induces profound sedation, often leading to extreme lethargy and a constant feeling of sleep deprivation. Higher doses may prompt complete unconsciousness, leaving individuals feeling excessively tired the following day.

• Spontaneous Bodily Sensations: Users typically experience a warm, pleasurable tingling sensation throughout their body, accompanied by mild throbbing or aching sensations.

• Tactile Hallucination: Unique tactile hallucinations manifest as structured vibrations and pulsations across the skin, extending outward for a short distance.

• Changes in Felt Gravity: Perception of gravity may be altered, contributing to feelings of heaviness or lightness.

• Motor Control Loss: Engaging in physical activities may result in a distinct loss of motor control, akin to walking on a trampoline.

• Appetite Enhancement: Mirtazapine induces intense appetite enhancement, comparable to the effects of cannabis.

Cognitive Effects

• Thought Deceleration: Cognitive processes slow down, leading to a sense of mental sluggishness.

• Analysis Suppression: Critical thinking and analytical abilities are diminished.

• Cognitive Euphoria or Dysphoria: Reports vary, with some users experiencing mild euphoria while others describe a neutral or dysphoric state of mind due to pronounced side effects.

• Dream Potentiation: Dreams become more vivid than usual, potentially contributing to enhanced dream recall.

• Conceptual Thinking: Despite cognitive impairment, users may experience enhanced conceptual thinking.

• Amnesia: Forgetfulness or memory impairment may occur.

• Immersion Enhancement: Engagement with external stimuli may become more immersive.

• Time Distortion: Perception of time may become distorted, leading to a sense of time dilation or contraction.

• Increased Music Appreciation: Users may experience heightened appreciation for music.

• Irritability: Some individuals may experience increased irritability.

• Emotion Suppression: Mirtazapine dulls emotions, making it difficult to express them.

• Anxiety Suppression: Mirtazapine's anxiety-suppressing effects are rapid and potent, surpassing those of selective serotonin reuptake inhibitors (SSRIs).

Visual Effects

• Distortions: Visual perception may be distorted, leading to alterations in size, shape, or color of objects.

• Visual Acuity Suppression: Visual acuity may decrease, resulting in blurred vision.

• Tracers: Persistent trails or afterimages may accompany moving objects.

• Drifting: Static objects may appear to warp, flow, or morph.

• Color Tinting and Shifting: Colors may appear altered or shift in hue.

• Symmetrical Texture Repetition: Patterns or textures may repeat symmetrically.

• Visual Haze: Visual clarity may be diminished, resulting in a hazy or foggy appearance.

Exploring Hallucinatory States

• External Hallucination: Delirious tactile hallucinations and visual disturbances may occur, resembling experiences with deliriants but less consistent and typically observed at high doses.

• Internal Hallucination: Spontaneous hypnagogic scenarios may manifest as one falls asleep, characterized by bizarre and nonsensical plots.

Understanding these effects and their potential combinations is essential for informed and safe use of mirtazapine.

FAQ (Frequently Asked Questions)

Is mirtazapine habit-forming?

No, mirtazapine is not habit-forming when used as a hallucinogen. In fact, the desire to use it may decrease with continued use. It is most often self-regulating.

What are the dangers of mirtazapine overdose?

While mirtazapine is considered relatively safe in the event of an overdose, it can still pose risks. Fatalities have been reported with overdose, although it is less toxic compared to other antidepressants. It is essential to use harm reduction practices and seek medical attention if overdose is suspected.

Can mirtazapine interact with other medications?

Yes, mirtazapine can interact with other medications, particularly other antidepressants. Combining mirtazapine with certain drugs may lead to adverse effects or serotonin syndrome. It's crucial to consult a healthcare professional before combining medications.

What is the legal status of mirtazapine worldwide?

Mirtazapine is legally approved for medical purposes worldwide. However, it is illegal to sell and possess in most countries without a prescription. The specific legal status may vary by country, so it's important to research local regulations.