The Addicted Brain
Presented by Larry Woodruff, M.S. Ed. [email protected] Expert Resources
• Bruce Lipton, Ph.D. Cell biologist, former professor at University of Wisconsin School of Medicine Author and speaker • William Lovallo, Ph.D. Professor of psychiatry and behavioral sciences at University of Oklahoma • Jeanette Norden, Ph.D. Professor of cell and developmental biology Vanderbilt University
Expert Resources
• Richard Restak, M.D. Clinical Professor of Neurology George Washington University School of Medicine and Health Sciences • Robert Sapolsky, Ph.D. Professor of Neurology and Neurosurgery Stanford University • Brian Luke Seaward, Ph.D. Author of many books on stress and holistic health. Founder and CEO of Inspiration Unlimited.
Brain Facts • Adult brain contains ~86 billion neurons • Each neuron makes up to 10,000 connections • Adult brain makes up <3% of total body mass, but uses 20-25% of total body energy (6 kcals/billion neurons/day. • In the womb synaptic connections formed at 1million/second • By first month of life a quadrillion connections have formed
Brain Facts
• The human cortex contains ~16 billion neurons…More neurons than the cortex of any other animal on the planet. • ~Age 25 the Prefrontal cortex finally matures, and we achieve full potential for rational judgment
• Women more prone to addiction than men Physiology of the Neural Impulse
Neurons Basics of Neural Transmission
• Dendrites receive input from other neurons • If the combined excitatory input reaches a threshold level, an electrical impulse is generated by the neuron (at the axon hillock) and it travels down the axon to the axon terminals • At that point the electrical signal releases chemical molecules (neurotransmitters) that flow into the tiny gap between that neuron and other neurons (called the synapse) and bind with specific receptors (special form of protein molecules) on the dendrites of those other neurons. Basics of Neural Transmission
• If enough neurotransmitters bind with enough receptors on another neuron, that neuron generates an impulse (called an “action potential”) • And so on • The critical elements in neuron communication in the brain, and throughout the body, are neurotransmitters and receptors Neurotransmitters Neurotransmitters ~ Facts
• Each NT can have vastly different functions in different neurons • The neurotransmitter doesn’t change • Different functions are determined by different receptors • There are 16 different subtypes of serotonin receptors, and several types of receptors for most other NT’s
Limbic System ~ Reward Pathway
Ventral Tegmental Area (VTA) • Receives sensory input, and attaches pleasure feeling/emotion. Heavy concentration of dopamine neurons. • Primary producer of dopamine in the brain, along with substantia nigrae • Heavily influences nucleus accumbens Limbic System ~ Reward Pathway
Nucleus Accumbens
• Receives dopamine neurons from VTA • This is the primary brain area associated with addiction • Relays pleasure signals to areas of cortex Mid Forebrain Bundle cortex Dopamine Neurons
• These are neurons that have dopamine as their neurotransmitter • They can only communicate with other neurons that have specific receptors for dopamine in the cell membrane of their dendrites • REMEMBER….Dopamine neurons in certain areas of the brain (the reward pathway) produce the sensation of pleasure, and are stimulated by all addictive substances
Dopamine Connection
• The pleasure signals from increased dopamine in the synapses of thousands of neurons in the Nucleus Accumbens and the Ventral Tegmental Area (the pleasure centers of your brain) are transmitted (via dopamine neuron axons) to neurons in the prefrontal cortex • Once the dopamine signals reach the cortex, we become aware of intense pleasure
Mid Forebrain Bundle cortex Opium and its Derivatives
OPIUM
CODEINE MORPHINE THEBAINE
Dilaudid Oxymorphine Percodan (oxycodone)
Hereoin Etorphine Opiate / Dopamine Connection
• Narcotics a.k.a. Opiates act on opiate receptors on brain neurons that have both opiate and dopamine receptors • There is a complex interaction between opiate receptors and dopamine receptors, such that when opiate receptors are stimulated, they facilitate the binding of dopamine to dopamine receptors on the same neuron. • Other types of addictive drugs will directly stimulate dopamine receptors
Key Neurotransmitters
Endorphins • Means “the morphine within” • Effective pain suppression • Mild euphoria • Implicated in runner’s high
Key Neurotransmitters
Endorphins • Opiates stimulate the same receptors as endorphins, only more effectively • Taking opiates suppresses the production of endorphins (our natural pain killers) RESULT – • Natural pain suppression is destroyed and is slow to recover • Withdrawal from long term use of opiates is very painful
Reticular Formation
• Reticular formation sends projections all over brain Reticular Formation
Large system with 110 nuclei • Plays a role in controlling heart rate • Contains respiratory center (medulla) • Respiratory center sends nerve fibers down spinal cord to diaphragm and to intercostal muscles and stimulates them to contract causing lungs to fill with air • This can be shut down by central nervous system depressants such as narcotics and alcohol, and is what causes overdose deaths.
Cocaine / Dopamine Connection
• Cocaine, on the other hand, does not directly increase dopamine release into the synapse. • Instead it binds with reuptake proteins (magenta colored structures on next slide) • Reuptake proteins act like vacuum cleaners sucking the dopamine molecules out of the synapse and recirculating them back into the sending neuron, thereby not allowing dopamine to bind with dopamine receptors on the receiving neuron for very long. Reuptake proteins
Dopamine molecules
Post Synaptic Receptors Cocaine Molecules blocking reuptake proteins Cocaine / Dopamine Connection
• RESULT…. • Cocaine blocks the reuptake of dopamine, so more dopamine stays in the synapse longer • So….dopamine receptors on the receiving neuron get super stimulated • Bottom line…. Cocaine causes a massive increase in dopamine activation….and therefore the sensation of pleasure
THC / Dopamine Connection
• Compare the areas of the brain affected by opiates to those affected by THC (active ingredient in marijuana) • The next slide illustrates that THC affects even more brain areas than opiates and cocaine • Note the cerebellum….a critical brain area in balance and coordinated movement
THC / Dopamine Connection
• The interaction with THC, THC receptors, and dopamine receptors is complex
• Much like the interaction of opiates, opiate receptors, and dopamine receptors
Brain Areas Adversely Affected by Marijuana Pleasure Neurotransmitters
Dopamine and addictive substances • Dopamine receptors decrease in number and sensitivity with long term use of psychoactive substances • Decreased sensitivity can become permanent, resulting in permanent decrease in ability to experience pleasure with normal activities Dopamine Pathways
• TI system connects hypothalamus to pituitary • ML system= pleasure producer – VTA to NA to frontal cortex • Nigrostriatal = basal ganglia & motor control Motor Cortices Control of Coordinated Movement
• The motor cortex is constantly receiving excitatory input from the cerebellum, and inhibitory input from the basal ganglia
• Coordinated movement relies on balancing the excitatory and inhibitory messages received by the motor cortex
• Alcohol and other CNS depressants impair the cerebellum, and motor cortex. The greater the BAC the greater the impairment.
• Result….. uncoordinated movements beyond conscious control Control of Coordinated Movement Basal Ganglia Key Neurotransmitters
Dopamine and motor control
• Basal Ganglia work with cerebellum for fine motor control • Shortage of dopamine in 2 basal ganglia causes Parkinson’s disease
Pleasure Neurotransmitters
Norepinephrine • Vastly different functions in different areas of brain and nervous system • Sensation of pleasure in VTA and nucleus accumbens • Produced in Locus Coeruleus from dopamine • Works either with dopamine or separately to create sensation of pleasure
Pleasure Neurotransmitters
Norepinephrine • Shortage of NE in pleasure pathways implicated, in part, in clinical depression • NE therefore mood enhancer • Depression associated with insufficient serotonin, dopamine, and norepinephrine; serotonin appears to be most significant. • NE also involved in arousal and attention in several brain areas • Also a hormone secreted by adrenals
Key Neurotransmitters
Serotonin (5HT) • All brain serotonin produced by Raphe Nuclei in reticular formation • Axons project to all areas of brain • 16 types of serotonin receptors in brain • Serotonin’s effects depend on the type of receptor it binds with.
Key Neurotransmitters
Serotonin • Helps induce sleep • Mood enhancer • Imbalances in thalamus and certain cortical areas create hallucinations …causes can be sleep deprivation, sensory deprivation, fasting, hallucinogens
MDMA
Effects of MDMA on Serotonin Activity : • MDMA occupies transporter proteins • Prevents the reuptake of serotonin back into the sending neuron Results : • More serotonin in synapse to bind multiple times with receptors on receiving neuron • Multiply this by thousands of neurons at once
Key Neurotransmitters
Serotonin
• Low levels in PFC associated with depression • Below normal levels in OCD • Below normal levels prior to menstruation in women with severe PMS Key Neurotransmitters
Serotonin • Ability to elevate serotonin levels rapidly and dramatically predicts dominance in some monkeys (with 100% certainty), when subordinate males compete for dominance. • Leaders on male sports teams and fraternities have high serotonin levels Limbic System Limbic System Anatomy
Largest integrative brain system • Hippocampus • Amygdala • Ventral Tegmental Area (VTA) • Nucleus Accumbens • Thalamus • Hypothalamus • Cingulate Gyrus • Entorhinal Cortex • Prefrontal Cortex • Orbitofrontal Cortex
Limbic System ~ Thalamus
• Hallucinogens, fasting, & sleep deprivation can affect serotonin receptors in Thalamus, and certain areas of the cortex. • Causes excess and erratic flow of information to and from some areas of cortex • Result = hallucinations and perceptual distortions
Thalamus is the red oval area in left image
Cortex Cortex
Prefrontal Cortex (executive function) • Sensory information fully processed, analyzed, and judged • This is responsible for logic, reasoning, creativity, imagination. Mid Forebrain Bundle cortex Cortex
Orbitofrontal Cortex • Located behind eyes • Involved in impulse control • Controls our ability to appreciate the consequences of our behaviors • Allow us to internalize cultural customs, laws, rules Our Conscience • Hijacked by most addictive drugs Autonomic Nervous System Autonomic Nervous System
• Regulates vital organs • HR • BP • Respiration • Temperature • Digestion • Operates subconsciously most or all of the time Autonomic Nervous System
Two major divisions:
• Sympathetic NS • Parasympathetic NS Both activated by hypothalamus and pituitary Brain stem acts as a relay
Sympathetic N.S.
• Stimulates fight or flight responses • Neurotransmitters Epinephrine (adrenaline) Norepinephrine (noradrenaline) Sympathetic N.S.
• Dilated pupils • Increased heart rate and blood pressure • Increased respiration • Increased strength and endurance • Decreased saliva • Decreased gastric secretions
Parasympathetic N.S.
• Calming and relaxing effect Opposite of SNS
• Neurotransmitter Acetylcholine
Parasympathetic N.S.
• Constricts pupils • Increases saliva • Decreases HR • Decreases BP • Increases gastric activity Drug Effects on the ANS
• All stimulants will increase SNS activity • All Narcotic Analgesics will increase PSNS activity • Because opiates (narcotics) constrict pupils, one can often identify users of heroin or other opiates by their pinpoint pupils Pamela Peeke, M.D.
• Authority on healthy lifestyle issues • Expert on hunger issues and food addiction
• Author of The Hunger Fix, and numerous other best selling books on health and nutrition issues
• Author of The Dopamine Made Me Do It article. Evidence for Food Addiction
• Highly addictive (hyperpalatable) foods = foods high in sugar, starch, fats, and salt. • 90% of dopamine neurons in the Ventral Tegmental Area (VTA) become stimulated when we are about to eat • VTA then stimulates the Nucleus Accumbens, the amygdala, and the hippocampus Evidence for Food Addiction
• Wang et al., 2001 Obese individuals had far fewer dopamine receptors in reward circuit. Thus had to eat more to experience same level of pleasure as average weighted individuals • Alsio et al., 2010 Studies of rats indicated that decrease in dopamine receptors caused by consumption of hyperpalatable foods instead of normal rat chow.
Evidence for Food Addiction
• Yale researchers (Gearhardt et al., 2011) Functional MRI studies indicate that both lean and obese women who demonstrated addictive behavior around food show same pattern of neural activity in brains as chronic drug abusers. • Nora Volkow, 2008 Obese individuals with fewer dopamine receptors also have less activity in Prefrontal Cortex. So less ability to control cravings, and stop after just a little bit.
Evidence for Food Addiction
• “Animal studies reveal that hyperpalatable diets, and sweet ones in particular, are more rewarding – and potentially more addictive – than intravenous cocaine and heroin (Ahmed 2012).” • “Once the rats become addicted to sugar, they are for more eager to gobble up amphetamines, alcohol, and cocaine in huge quantities – and they become almost instantly addicted to those substances as well (Johnson & Kenny, 2010). Epigenetics and Addiction
• Stress has been shown to “switch on” genes for obesity, and addiction. • There is a close connection between stress and addictive behaviors. • Research on Agouti Mice shows that supplementing diets with methyl donors can switch off the agouti gene for obesity and yellow fur.