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 Methadone is dual action synthetic opioid analgesic. While agonism (activation) of the µ-opioid receptor is the primary mechanism of action for the treatment of pain, methadone also acts as an agonist of κ- and σ-opioid receptors within the central and peripheral nervous systems.   

The end result is decreased nerve conduction and reduced neurotransmitter release, which blocks the perception of pain signals and stops withdrawal. Methadone also acts as an antagonist (blocker) at the NMDA receptor, reducing calcium influx and neuronal excitability. This reduces opioid tolerance development while dampening   nerve excitability and suppresses the physical symptoms of withdrawal. 

 Buprenorphine is a semi-synthetic opioid with mixed receptor activity. Its primary action is partial agonism at the μ-opioid receptor, providing sufficient receptor activation to reduce pain transmission and prevent withdrawal while limiting maximal opioid effects due to its ceiling activity. Buprenorphine also functions as a potent antagonist at the κ-opioid receptor, which reduces dysphoria, stress signaling, and hyperalgesia associated with κ-receptor activation. In addition, it has very high affinity and slow dissociation from the μ-opioid receptor, resulting in sustained receptor occupancy. The net effect is reduced neuronal excitability, diminished perception of pain, and effective suppression of physical withdrawal symptoms.

 As a full μ-opioid receptor agonist, it has the same pharmacologic mechanism responsible for the “high” associated with other opioids; however, its long half-life, slow onset, and steady receptor activation blunts the rapid dopamine surge that typically drives intoxication. As a result, when methadone is properly used, it stabilizes neurophysiology and relieves withdrawal or pain without causing a high. 

Euphoria is more likely in opioid-naïve individuals, at very excessive doses, or when mismanaged/misused, which is a very significant threat to the individual's life because, unlike all opioids that are frequently used recreationally,  methadone accumulate in the body and remains for an extended period of time which can lead to delayed respiratory depression even in the absence of an initial intoxicating effect. 

Addiction counseling is a structured, evidence-based therapeutic process aimed at treating substance use disorders by addressing both the neurobehavioral and psychosocial components of addiction. It involves the use of clinical interventions, such as motivational interviewing, cognitive behavioral therapy, relapse prevention strategies, and trauma-informed care, to help individuals understand patterns of substance use, modify maladaptive behaviors, and develop sustainable coping skills. 

Addiction counseling also focuses on reinforcing recovery-supportive behaviors and improving emotional regulation with the goal of restoring functional stability and supporting long-term recovery.  Addiction counseling also involves providing support for families and a host of real-world services, such as financial, educational, and vocational counseling to name a few.