Phenibut & Injectable opiates
Phenibut is a derivative of gamma-aminobutyric acid (GABA), a neurotransmitter that reduces neuronal excitability and promotes relaxation. It crosses the blood-brain barrier more effectively than GABA itself due to the addition of a phenyl ring, which enhances its lipophilicity. Once inside the brain, phenibut binds primarily to GABA-B receptors, although it may also have weak activity on GABA-A receptors.
The activation of GABA-B receptors leads to inhibitory effects in the central nervous system, dampening neural excitability and reducing stress responses. This results in anxiolytic (anti-anxiety), sedative, and muscle-relaxing effects. In addition, phenibut influences dopamine levels, particularly in regions like the striatum, where it can enhance dopamine transmission. This action may contribute to mood enhancement, motivation, and mild euphoria reported by users. At higher doses, this dopaminergic modulation can lead to stimulant-like effects, making it paradoxically both relaxing and energizing in some cases.
Phenibut also affects the hypothalamic-pituitary-adrenal (HPA) axis by reducing the release of stress hormones such as cortisol, which further contributes to its calming properties. It decreases arousal in circuits related to the fear response, making it useful in situations involving social anxiety or general anxiety. However, its mechanism is slow-acting compared to typical sedatives like benzodiazepines, which target GABA-A receptors more directly.
Injectable opiates, such as heroin, morphine, and fentanyl, work by binding to opioid receptors in the central and peripheral nervous systems. These receptors are primarily classified as mu (μ), kappa (κ), and delta (δ) receptors. The most important in terms of the euphoric and analgesic effects of opiates is the mu-opioid receptor. When these drugs are injected, they enter the bloodstream and quickly cross the blood-brain barrier, leading to a rapid onset of effects.
Upon reaching the brain, opiates bind to mu-opioid receptors located in areas such as the ventral tegmental area, nucleus accumbens, and the periaqueductal gray. Activation of these receptors reduces the release of neurotransmitters like GABA, which normally inhibit the activity of dopamine neurons. This disinhibition results in a flood of dopamine in the reward circuits, producing intense euphoria and pleasure. The speed of onset and intensity of the euphoria depend on the pharmacokinetics of the substance. For example, heroin is rapidly metabolized to morphine after crossing the blood-brain barrier, leading to a sudden, powerful “rush,” while morphine has a slower onset of action but still binds effectively to the same receptors.
Opioid receptor activation also reduces the transmission of pain signals by inhibiting the release of excitatory neurotransmitters like substance P and glutamate in the spinal cord and brain. This creates powerful analgesia, which is one reason these drugs are used in medical settings for severe pain. Additionally, they affect the brainstem, slowing respiration by suppressing the respiratory center. This action can become dangerous or fatal, especially with high doses or in combination with other central nervous system depressants like alcohol or benzodiazepines, leading to respiratory arrest.
Beyond euphoria and analgesia, opiates affect other systems as well. They slow down gastrointestinal motility by acting on opioid receptors in the gut, often causing constipation. They also influence the hypothalamic-pituitary axis, leading to reduced secretion of hormones like testosterone, which can cause sexual dysfunction and decreased libido. In some individuals, opiates induce nausea and vomiting by triggering the chemoreceptor trigger zone in the brain.
Combining phenibut and injectable opiates can lead to significant risks due to overlapping effects on the central nervous system. When used together, these drugs can amplify each other’s depressant effects, heightening the risk of heavy depression, which can be life-threatening.
This combination also increases the likelihood of cognitive impairment, as noted with other GABAergic substances like pregabalin when combined with opioids. Users report diminished euphoria from opiates when taking phenibut, which may reflect a shift in neurotransmitter activity or receptor sensitivity. Anecdotal evidence suggests that the combination can cause emotional numbness and anhedonia, potentially dulling the ability to feel pleasure from other rewarding activities. Some individuals experience mood instability or irritability when withdrawing from either substance, which can worsen during concurrent use.
Respiratory depression is a particularly severe risk, especially since both phenibut and opioids slow breathing. Clinical data on the potentiation of opioids by GABAergic agents indicate that even moderate doses can dangerously impair breathing. This combination also appears to increase tolerance and dependence more rapidly, requiring escalating doses to achieve the same effects, which further exacerbates the risk of overdose. Harm reduction strategies strongly advise against mixing these substances due to their synergistic dangers, similar to combining opiates with benzodiazepines or alcohol.
Of course, the mechanisms of action and the severity of the depressant effect of phenibut are not comparable to the action of more classic and pronounced depressants. However, the general vector and more generalized action give grounds for giving more cautious recommendations. In general, this combination can be called one of the little-studied, so we will be grateful for any information about it.
All things considered, we recommend avoiding this combination.
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