The Pharmacology of Feeling Good: What Produces the High Feeling?

October 10, 2025 •

4 min read

Every type of reward-seeking behavior that has been studied increases the level of dopamine transmission in the brain [1.5.3]. Psychoactive drugs hijack this natural process, and understanding what produces the high feeling involves looking at how these substances manipulate key neurochemicals to create intense euphoria [1.4.7, 1.3.2].

Quick Summary

The euphoric 'high' from medications results from a massive surge of neurotransmitters like dopamine in the brain's reward circuit [1.2.2]. Different drugs manipulate this system in unique ways, leading to powerful feelings of pleasure and reinforcement.

Key Points

The Core Mechanism: The 'high' feeling is primarily produced by a massive, artificial surge of neurotransmitters like dopamine in the brain's mesolimbic reward pathway [1.3.2, 1.2.2].
Dopamine's Role: While once thought to directly cause euphoria, scientists now believe dopamine is more responsible for motivation and reinforcing the 'wanting' of a drug, while other systems like endorphins may mediate the 'liking' [1.5.1, 1.2.2].
Diverse Drug Actions: Different drug classes—stimulants, opioids, cannabinoids—use unique pharmacological mechanisms to ultimately flood the reward system with dopamine [1.4.1, 1.2.2].
Stimulants vs. Opioids: Stimulants directly increase dopamine in the synapse by blocking its reuptake or forcing its release, while opioids remove the inhibitory 'brakes' on dopamine-producing neurons [1.2.2].
Brain Adaptation: Chronic drug use causes the brain to adapt by reducing its sensitivity to dopamine, diminishing the high and the ability to feel pleasure from natural rewards [1.6.4].
Beyond Dopamine: Other neurotransmitters like serotonin (targeted by MDMA) and GABA (affected by alcohol) also play crucial roles, shaping the specific qualities of the euphoric experience [1.4.6, 1.2.2].
Addiction Cycle: The process of seeking a high leads to tolerance and withdrawal, where drug use shifts from seeking pleasure to avoiding the discomfort of a dopamine-deficient state [1.6.2].

The Brain's Natural Reward System

The human brain possesses a sophisticated network of structures known as the reward system, with the mesolimbic pathway at its core [1.6.2]. This system is designed to reinforce behaviors essential for survival, such as eating, socializing, and exercising [1.6.4]. When we engage in these activities, the brain releases chemical messengers called neurotransmitters, primarily dopamine, which creates a sense of pleasure [1.5.4]. This pleasurable sensation motivates us to repeat the behavior [1.5.1]. Key brain regions involved include the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex [1.2.2]. The VTA produces dopamine, which is then released into the NAc and other areas, signaling that a rewarding event has occurred [1.3.1]. Scientists now believe that dopamine is less about directly causing pleasure and more about motivation and reinforcing the memory of a pleasurable activity, making you 'want' to do it again [1.5.1, 1.2.2]. The actual feeling of 'liking' or euphoria may be more closely mediated by the body's natural opioids (endorphins) and GABAergic systems [1.2.2].

How Medications Hijack the System

Psychoactive substances produce a 'high' by artificially manipulating this delicate system, causing surges of neurotransmitters far greater than those produced by natural rewards [1.5.1, 1.6.4]. This intense over-activation is what makes the drug-induced high so powerful and reinforces drug-taking behavior [1.6.4]. Different classes of drugs have distinct mechanisms of action, but they all ultimately converge on the brain's reward pathway, primarily by increasing the amount of dopamine in the synapse [1.6.6].

Stimulants (Cocaine, Amphetamines)

Stimulants like cocaine and amphetamines directly target the dopamine system. Cocaine works by blocking dopamine transporters, the molecules responsible for recycling dopamine back into the neuron. This blockage causes dopamine to build up in the synapse, enhancing its pleasurable signal [1.4.6, 1.2.2]. Amphetamines are even more direct; they not only block reuptake but also enter the neuron and force the release of dopamine, causing an even more significant flood [1.2.2, 1.4.6]. This massive increase in dopamine correlates directly with the intensity of the reported euphoria [1.2.2].

Opioids (Heroin, Morphine, Fentanyl)

Opioids mimic the body's natural pain-killing and pleasure-inducing chemicals, the endorphins [1.7.3]. They bind to specific opioid receptors, particularly the mu-opioid receptors, located on inhibitory neurons in the VTA [1.2.2, 1.6.6]. By activating these receptors, opioids prevent the inhibitory neurons from firing. This action 'removes the brakes' on the dopamine-producing neurons, causing them to release more dopamine into the nucleus accumbens and producing a powerful wave of euphoria and pain relief [1.2.2, 1.2.4].

Other Drug Classes

Cannabinoids (THC): The primary psychoactive component in marijuana, THC, activates cannabinoid (CB1) receptors in the brain. These receptors are involved in modulating the release of other neurotransmitters. By activating CB1 receptors on inhibitory neurons, THC can lead to an increase in dopamine firing in the reward pathway, contributing to the high [1.2.4, 1.2.2].
Alcohol: Alcohol has complex effects, interacting with multiple neurotransmitter systems. It enhances the activity of GABA, the brain's primary inhibitory neurotransmitter, leading to feelings of relaxation [1.2.2]. It also causes an increase in dopamine release in the nucleus accumbens, contributing to its rewarding effects [1.2.4].
Serotonergic Drugs (MDMA): While dopamine is central to wanting and reinforcement, other neurotransmitters shape the qualitative experience of the high. MDMA (ecstasy), for example, causes a massive release of serotonin, in addition to dopamine and norepinephrine [1.4.1]. This serotonin surge is largely responsible for the feelings of emotional closeness, empathy, and elevated mood characteristic of the drug [1.4.1, 1.4.6].

Comparison of Drug Classes and Their Euphoric Effects


Drug Class	Primary Mechanism	Key Neurotransmitters	Characteristics of the 'High'
Stimulants	Block dopamine reuptake / promote dopamine release [1.4.6]	Dopamine, Norepinephrine [1.2.2]	Intense euphoria, energy, alertness, increased confidence [1.4.6].
Opioids	Activate opioid receptors, disinhibiting dopamine release [1.2.2]	Dopamine, Endogenous Opioids [1.2.4]	Powerful rush of pleasure, pain relief, sedation, calm [1.2.4, 1.4.5].
Cannabinoids	Activate cannabinoid (CB1) receptors, indirectly increasing dopamine [1.2.2]	Dopamine, Endocannabinoids [1.2.4]	Relaxation, euphoria, altered perception of time and senses [1.4.2].
Alcohol	Enhances GABA activity, increases dopamine release [1.2.2]	GABA, Dopamine, Glutamate [1.2.4]	Relaxation, disinhibition, euphoria followed by sedation [1.2.2].
Empathogens	Promote massive serotonin release [1.4.1]	Serotonin, Dopamine [1.4.6]	Emotional openness, empathy, energy, enhanced sensory perception [1.4.5].

Long-Term Effects and Conclusion

Repeatedly hijacking the brain's reward system with drugs leads to profound, long-lasting adaptations. The brain compensates for the overwhelming dopamine surges by reducing the number of dopamine receptors or producing less dopamine naturally [1.6.3, 1.6.4]. This is known as tolerance, and it means the user needs more of the drug just to feel normal, let alone high. The ability to feel pleasure from natural rewards diminishes, leading to a state of anhedonia (the inability to feel pleasure) [1.6.4]. This creates a vicious cycle of withdrawal and compulsive use [1.6.2].

In conclusion, the 'high' feeling produced by medications is a complex neurochemical event centered on the artificial overstimulation of the brain’s innate reward pathway. While the immediate sensation is one of intense pleasure, the long-term pharmacological consequences involve significant and often detrimental changes to brain structure and function, fundamentally altering the user's relationship with natural pleasure and motivation.

For more information, visit the National Institute on Drug Abuse (NIDA).

Frequently Asked Questions

The main chemical messenger associated with the 'high' is dopamine. Drugs of abuse cause a massive increase in dopamine activity in the brain's reward circuit, which is far more intense than the release from natural rewards like food or social interaction [1.2.2, 1.3.2].

No. While most abused drugs increase dopamine, other neurotransmitters they affect create different experiences. For instance, opioids produce a sedating, warm euphoria, while stimulants like cocaine cause an energetic, alert high. Drugs like MDMA produce feelings of empathy by targeting the serotonin system [1.4.5, 1.4.6].

Drugs hijack and over-activate the brain's reward circuit, causing surges of dopamine and other neurotransmitters that are much larger and last longer than those from natural rewards like eating or socializing. This intensity powerfully reinforces drug-taking behavior [1.5.1, 1.6.4].

Endorphins are the body's natural opioids and are primarily involved in pain relief and a sense of well-being (the 'liking'). Dopamine is more strongly associated with motivation, reinforcement, and craving (the 'wanting'). Opioid drugs mimic endorphins and also cause a massive release of dopamine, combining both effects powerfully [1.7.3, 1.2.2].

With repeated use, the brain adapts to the excessive dopamine. It may reduce the number of dopamine receptors or produce less of the neurotransmitter. This leads to tolerance (needing more of the drug for the same effect) and a diminished ability to feel pleasure from everyday activities [1.6.4, 1.2.7].

Nearly all drugs with addiction potential increase dopamine in the brain's reward pathway, which is considered a final common pathway for reinforcement. They may do this through different direct or indirect mechanisms, but the effect on dopamine is a shared characteristic [1.6.6, 1.3.6].

The reward pathway, also known as the mesolimbic dopamine system, is a circuit in the brain that controls responses to natural rewards like food and sex. It includes the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Activation of this pathway reinforces behaviors necessary for survival [1.3.1, 1.2.2].