Psychoactive Agents

1. Psychoactive Agents Stimulants Psychodelics

2. Psychoactive stimulants • Stimulants: • activate the central nervous system to produce • arousal, • increased alertness, • elevated mood • Typically affect dopamine, norepinephrine and serotonin • Several drugs in this category • Cocaine • Amphetamine • Methamphetamine • Ritalin, Adderal, and most ADHD medications • Ephedrine

3. Psychoactive stimulants • Cocaine, • extracted from the South American coca plant, • produces • Euphoria • decreases appetite, • increases alertness • relieves fatigue. • Cocaine blocks the reuptake of dopamine and serotonin at synapses, • Potentiating effect of these neurotransmitters • Makes neurotransmitter remain longer in synapse. • Presumably, cocaine produces euphoria and excitement because dopamine removes the inhibition the cortex usually exerts on lower structures.

4. Cocaine user Normal

5. Psychoactive Drugs • Amphetamines • group of synthetic drugs • Again produce euphoria • increase confidence • In low doses: increases concentration. • increase the release of norepinephrine and dopamine • Common examples: • Amphetamine (Adderal®); Dextroamphetamine (Dexedrine®, Dextrostat®) • Methamphetamine (Desoxyn®) • Highly related:Ritalin: • Ritalina, Rilatine, Attenta, Methylin, Penid, Rubifen); and the sustained release tablets Concerta, Metadate CD, Methylin ER, Ritalin LA, and Ritalin-SR. Focalin

6. Amphetamine Action • DA neurons release DA into the synapse: From there 1 of 3 things can happen: • DA can then attach to the post-synaptic membrane • DA can be degraded by enzymes • DA can be taken back up by the pre-synaptic membrane. • Amphetamine appears to affect all three mechanisms: • Promotes release of DA into the synapse • Inhibits the DA degredative enzyme, monoamine oxidase (MAO), • Blocks the uptake proteins in the pre-synaptic membrane • The result : Amphetamine effectively promotes a flood of DA into the brain reward center: • Nucleus Accumbens or Nac • This area is highly involved in both learning and reward.

7. Amphetamine Action • Amphetamine and related compounds elicit a variety of dose-dependent deleterious effects. • low doses of AMPH may • improve attention • improve vigilance • At high doses: • over-stimulation of the motor and cognitive systems • behavioral stereotypy, repetitive thoughts and even hallucinations. • In rodents, a high AMPH dose elicits behavioral stereotypy: • continuous digging • Searching • Licking • Gnawing • Circling • In humans, high doses of AMPH may elicit: • psychotic state, • High rates of locomotion and repetitive behavior • high potential for self-injury or injury to others

8. A normally moving rat

9. A rat given 8.0 mg/kg amphetamine

10. Psychoactive Drugs: Nicotine • Nicotine: • primary psychoactive and addictive agent in tobacco • Also in chewing tobacco, nicotine gum, etc. • It stimulates nicotinic acetylcholine receptors. • In the periphery, • it activates muscles • may cause twitching. • In CNS: • produces increased alertness • Also faster response to stimulation. • Given peripheral effects, why might individuals on antipsychotics or those with Parkinson’s like to smoke?

11. Psychoactive Drugs: Caffeine • Caffeine: • active ingredient in coffee, many soda pops; teas; energy drinks, etc. • produces arousal, increased alertness, and decreased sleepiness. • Cardiovascular response: direct stimulation of the heart • mitigated to some extent by concurrent vagal stimulation. • CNS + PNS effects sometimes result in ventricular irritability • Also get direct vasodilation with concurrent vasoconstriction from stimulation of the medulla • Result: either increases or decreases in blood pressure. • Smooth muscle is relaxed by caffeine, while skeletal muscle is stimulated. • Action: blocks receptors for the neuromodulator adenosine • This increases the release of dopamine and acetylcholine. • Because adenosine has sedative and depressive effects, blocking its receptors contributes to arousal • Acts like amphetamine in releasing DA.

12. PsychodelicDrugs • Psychedelic drugs: • compounds that cause perceptual distortions in the user. • May be referred to as hallucinogenic • Not really inducing hallucinations, but distortions in perception: • Light and color details are intensified, • objects may change shape, • sounds may evoke visual experiences, • light may produce auditory sensations. • Synesthesia: stimulation of one sensory or cognitive pathway leading to automatic, involuntary experiences in a second sensory or cognitive pathway

13. Psychoactive Drugs • lysergic acid diethylamide (LSD) • best-known psychedelic • is structurally similar to serotonin • stimulates serotonin receptors • Appears to disrupt the brain stem’s ability to screen out irrelevant stimuli. • psilocybin and psilocin • Another serotonin-like psychedelics • both derived from the mushroom,Psilocybemexicana • Mescaline • the active ingredient in peyote (the crown or button on the top of the peyote cactus), • psychedelic properties result from stimulation of serotonin receptors.

14. Psychoactive Drugs: Ecstasy • Ecstasy • street name for a drug developed as a weigh-loss compound • methlenedioxymethamphetamine (MDMA). • At low doses: • psychomotor stimulant • Increases energy, sociability, and sexual arousal. • At higher doses: • produces hallucinatory effects like LSD. • Also can overstimulate muscles resulting in “locked” or frozen muscles • MDMA stimulates • the release of dopamine which accounts for muscle and arousal effects • the release of serotonin, which probably accounts for the hallucinatory effects.

15. These brain sections have been stained with a chemical that makes neurons containing serotonin turn white. Photos in the top row are from a normal monkey; those below are from a monkey given MDMA a year earlier.

16. Psychoactive Drugs: PCP • Phencyclidine (PCP): • Developed as an anesthetic typically used by veterinarians • was abandoned for human use because it produces schizophrenia-like disorientation and hallucinations. • PCP increases activity in the dopamine pathways • This stimulates motivation system • Also, drug’s motivating properties apparently are partly due to its inhibition of a subtype of glutamate receptors.

17. marijuana • Marijuana • is the dried and crushed leaves and flowers of the Indian hemp plant, Cannabis sativa. • The major psychoactive ingredient is delta-9-tetrahydrocannabinol (THC) • . • THC actions: • THC binds with cannabinoid receptors, which ordinarily respond to endogenous cannabinoids. • Two known cannabinoids receptors: • anadamide • 2-arachidonyl glycerol, or 2-AG. • These receptors are found on axon terminals; • Unusual action: • cannabinoids are released by postsynaptic neurons • act as retrograde messengers, regulating the presynaptic neuron’s release of neurotransmitter.

19. Addiction • Reward refers to the positive effect an object or condition – such as a drug, food, sexual contact, and warmth – has on the user. • Drug researchers have traditionally identified the mesolimbicortical dopamine system as the location of the major drug reward system. • It takes its name from the fact that it begins in the midbrain (mesencephalon) and projects to the limbic system and prefrontal cortex. • The most important structures in the system are the nucleus accumbens, the medial forebrain bundle, and the ventral tegmental area.

20. Virtually all the abused drugs increase dopamine levels in the nucleus accumbens