We Do Science on Crack… with Cocaine and the Blood-Brain Barrier

A classic picture showing a line of cocaine, along with a rolled-up dollar bill.Root of All Evil

Goofball, candy, ice, crack, snow, weasel dust, Belushi, Charlie…  High in the Andes of South America, Erythroxylum coca grows as a shrub.  For 2,500 years at least, its leaves have been known and used for their stimulant properties.  Over 5 million people use cocaine and its derivatives in the United States alone.

Ancient Inca legends claimed that:

“… God’s angels had presented man with the coca leaf to satisfy the hungry, provide the weary and fainting with new vigour, and cause the unhappy to forget their miseries.”

Even the Spanish after their arrival in 1533 observed that:

“… The herb is so nutritious and invigorating that the Indians labour whole days without anything else, and on the want of it they find a decay in their strength…”

Typically, cocaine is snorted, smoked as “crack” by addicts, or dissolved and injected.

Symptoms after ingesting cocaine include euphoria, the urge to speak, enhanced libido, loss of inhibitions, hallucinations, dilated pupils, vasoconstriction, hypertension, tachycardia, and death from respiratory arrest.  Schizophrenic episodes may occur.

Cocaine induces strong psychic, but not physical, dependence.  The psychological consequences of cocaine abuse are:

  • Impairment of mental function

  • Low concentration and memory

  • Opinion is difficult and slow

  • Intelligence is reduced; previous knowledge can also reduce

  • Changes in mood

  • Will and desire are reduced.


What is Cocaine?

A close-up photograph showing a branch of the coca plant.Cocaine is one of a number of naturally occurring tropane alkaloids – the first commercial anaesthetic – found in the leaves of the coca plant.

This evergreen shrub is cultivated at high altitudes, especially in Bolivia, Colombia and Peru, but coca is also grown in parts of tropical Asia, such as Java and Sri Lanka.  Out of the four varieties of the genus, Erythroxylum coca var. coca is the only one to grow wild in the eastern Andes.

A slide describing the relatively simple chemical recipe for making cocaine hydrochloride. The caption reads: "Dissolve Coke Base in Diethyl Ether; Filter (Constitutes Solution A). Dissolve Concentrated Hydrochloric Acid in Acetone (Constitutes Solution B). Add Solution A to Solution B; Mix Thoroughly and Let Sit (Cocaine Hydrochloride Precipitates). Filter and Dry. Cocaine Hydrochloride."
Don’t try this recipe at home!

The extraction and isolation of this alkaloid from the coca leaf can be readily performed using a series of relatively unsophisticated techniques.

For basic street use purposes, the raw plant material is processed chemically as indicated:

Because it is soluble in water, cocaine hydrochloride is readily absorbed through the watery mucous membranes of the nose when it is insufflated (snorted).

Cocaine is a pyrogenic drug, augmenting heat production in stimulating muscular activity and causing vasoconstriction which decreases heat loss.  Small doses of cocaine slow the heart rate, but after moderate doses, the rate is increased due to central sympathetic stimulation.

A chemical equation showing how cocaine free base can be transformed into cocaine hydrochloride.

Adverse reactions to cocaine are systemic in nature and involve the central nervous system (CNS) and/or the cardiovascular system.  CNS reactions are excitatory and/or depressant, and may be characterized by nervousness, restlessness and excitement.

Tremors and eventually clonic-tonic convulsions may result.  Emesis may occur.  Central stimulation is followed by depression, with death resulting from respiratory failure.

Overdosing – What can be done?

Don’t wait.  Call 999.

The fatal dose of cocaine has been approximated at 1.2 gram, although severe toxic effects have been reported from doses as low as 20 milligrams.

The symptoms of cocaine poisoning are referable to the CNS, namely the patient becomes excited, restless, garrulous, anxious and confused. Enhanced reflexes, headache, rapid pulse, irregular respiration, chills, rise in body temperature, mydriasis, exophthalmos, nausea, vomiting and abdominal pain are noticed. In severe overdoses, delirium, Cheyne-Stokes respiration, convulsions, unconsciousness, and death from respiratory arrest result. Acute poisoning by cocaine is rapid in developing.

Specific treatment of acute cocaine poisoning involves the intravenous administration of a short-acting barbiturate or diazepam.  Artificial respiration may be necessary.  It is important to limit absorption of the drug.  If entrance of the drug into circulation can be checked, and respiratory exchange maintained, the prognosis is favourable since cocaine is eliminated fairly rapidly.

A chemical representation of the Hydrogen bonds in a Cocaine molecule.
The hydrogen bonds of a Cocaine molecule. Source: Puffthemutantdragon.wordpress.com

Because cocaine hydrochloride is an ionic compound, it is relatively soluble in water through the formation of hydrogen bonds.  Free base cocaine, however, cannot form hydrogen bonds so easily and is thus less soluble in water, but more soluble in fats.

In the human body, depending on many complex factors, bases can accept hydrogen ions and in other circumstances, hydrogen ions can be removed from salts.  This makes predicting the action of heroin and cocaine very difficult.

Drugs that are injected are usually injected in solution in water, and often in the form of the salt, like cocaine hydrochloride.

The intensity, duration and speed of action of drugs, such as cocaine or heroin on the central nervous system (CNS) is complex and partly relates to the ease with which a drug crosses the blood-brain barrier.  So, drugs that are less soluble in water more easily cross this barrier.


The Blood-Brain Barrier (BBB)

A diagram explaining the different types of ionic transports through the blood-brain barrier.
Different types of molecules can be transported through the Blood-Brain Barrier. Source: rsc.org

The control of cerebral blood flow is the most highly developed and sophisticated system in the body.

Blood from the brain drains into the jugular veins and returns to the heart via the superior vena cava.

Neural control is mainly via noradrenergic neurons in the cerebral cortex, which lead to vasoconstriction.  The cholinergic input, which has a vaso-dilatory action, is derived from the cranial nerves that innervate the face.

Because the brain is so susceptible to slight chemical imbalances, the need for homeostasisthe property of a system in which variables are regulated so that internal conditions remain stable and relatively constant – is greater in the brain than in any other organ.  Homeostasis in the brain is unique and depends on the functional capacity of the capillary networks that supply blood to the brain.

This image shows a section through a blood vessel in the brain of a mouse, seen under the microscope, as well as endothelial cells, surrounded by glial cells, and processed from surrounding brain cells.
The brain’s blood vessels are lined with endothelial cells that are wedged tightly together, creating a nearly impermeable boundary between the brain and bloodstream. This image shows a section through a blood vessel (black) in the brain of a mouse as well as endothelial cells (surrounded by glial cells in green) and processed from surrounding brain cells (in red). Source: brainfacts.org

The brain is able to absorb some substances, oxygen O2 and steroid hormones, but not others, because the capillary are especially adapted to create a protective barrier.  The brain capillaries have walls composed of endothelial cells joined by tight junctions.

This restricts the entry of potentially harmful substances.

The blood-brain barrier (BBB) is a network of tiny blood vessels or capillaries that separates the interior of the central nervous system (brain and spinal cord) from the rest of the body’s circulatory system.

This separation is required to help the brain maintain a stable internal environment and function properly.

The BBB also helps to protect the brain from infectious micro-organisms.



Capillaries are the body’s smallest blood vessels.  They sit at the junction between the arteries – which carry oxygen-bearing blood to various organs and tissues – and the veins, which carry oxygen-depleted blood and carbon dioxide waste from the organs and tissues to the heart, on the way to their eventual destination point in the lungs.

Gas exchanges of oxygen and carbon dioxide CO2 levels into the blood take place inside the capillaries.

A cartoon about the Blood-Brain Barrier man. When presented with unwelcome visitors, the BBB man says: "I'm sorry, but you are too highly charged, too large and lipid soluble. You cannot enter the brain!"
The blood-brain barrier protects the brain from unwanted visitors. Source: faculty.washington.edu

At the exception of the blood-brain barrier, the capillaries have relatively large openings in their walls that allow large and small molecules to move in and out of the bloodstream in every location around the human body.

This level of access means that any required substance produced in most of the body can easily travel through the bloodstream and get where it is needed.  However, it also means that conditions in the tissues fed by the capillaries can change rapidly and relatively chaotically as different molecules move in and out of circulation.

The central nervous system, and especially the brain, cannot handle the sorts of fluctuations that occur when all molecules can flow easily through the capillary walls.  Actually, these fluctuations would destabilise the brain to the point where it would not be able to perform its function as the body’s command and control centre. 

In addition, if any molecule could easily enter the central nervous system, then infectious micro-organisms could get to the brain and wreak all sorts of havoc on the organ’s structures and activities.

To help prevent these possibilities, the capillaries in the BBB are very tightly constructed and lack the large openings found in other capillaries.  Additionally, supporting cells (called astrocytes) sit in the barrier outside the capillary walls and further block any influx of unwanted molecules and micro-organisms.

Because the BBB is so well developed, many chemical substances that are essential for the brain, but which the brain cannot synthesise, i.e glucose and amino-acids, have to be transported across the barrier by active transport.  The only substances that pass passively across the blood-brain barrier are lipid-soluble ones, such as O2 and CO2, as well as nicotine, caffeine, alcohol and heroin.

Cocaine and methamphetamine can significantly damage normal function in the blood-brain barrier.  In turn, the damage can open up the brain to infection and other processes that can produce severe or life-threatening changes in brain health.


The Effects of Cocaine and Methamphetamine

A diagram showing how Cocaine affects Dopamine transporters at synapses.
The effect of cocaine on the dopamine receptors of synapses. Source: Reed.edu

Psychoactive drugs and neurotoxins may alter such properties of the brain’s neurons as the release and the re-uptake of a particular neurotransmitter, or the availability of its receptor binding sites on the target cell.

A drug, such as cocaine, acts partly by blocking the re-uptake of dopamine.

After the drug reaches the synapse, there is an abnormally high concentration of dopamine in the synaptic cleft, and receptors are flooded with dopamine.


Happy as Larry…

The high occupation of dopamine receptors can induce euphoria, which makes it the main appeal for those who take cocaine, or other psychoactive substances.

For a number of reasons having to do with how cell walls are constructed, molecules that dissolve easily in the presence of fat can pass directly through the capillary walls in the blood-brain barrier.  Among the molecules that can access the CNS in this way are cocaine and methamphetamine.

Once inside the central nervous system, these drugs produce mind alteration and a variety of other effects by altering the normal levels of certain neuro-transmitting chemicals – such as dopamine, norepinephrine and serotonin – that support proper brain function by passing on required messages between millions of nervous system cells, called neurons.


Hyperthermia, Not A Laughing Matter

An MRI (magnetic resonance imaging) brain scan.
Brain scan of a drug addict showing signs of hyperthermia.  Source: Drugrehab.us

One of the most unfortunate consequences of neurotransmitter alteration by cocaine and/or methamphetamine is a significant increase in the amount of heat retained inside the brain and body.  If heat levels get too high, they can trigger a condition called hyperthermia, which literally means “overheat.”

Hyperthermia can produce serious damage in the capillary walls inside the blood-brain barrier and lead to the formation of significant gaps that give access to dangerous molecules not usually allowed into the restricted environment of the CNS.


Significant BBB Damage

Apart from its role in hyperthermia, cocaine produces chemical changes in the capillary walls that lead to the formation of abnormally large points of entry through the BBB, according to a study published in 2010 in Blood, the journal of the American Society of Hematology.

These chemical effects are particularly prominent in cocaine users with HIV infections.  And the authors of the study believe that the relatively rapid advancement of HIV’s brain effects in cocaine users stems from the ability of both cocaine and HIV to damage the capillary structures in the blood-brain barrier.

Cocaine may also damage the BBB by increasing the flow of blood plasma to the brain, or by encouraging an excessive flow of the neurotransmitter serotonin from the body to the brain.

In addition to its role in hyperthermia, methamphetamine can apparently damage the blood-brain barrier through a direct, toxic effect on the capillaries within the barrier.

Free Base Cocaine

‘Crack’ or free base cocaine is highly addictive.

It is called free base to emphasise that it is not the salt, but the uncharged molecule.  When crack is smoked, it is inhaled and rapidly absorbed through the lungs into the bloodstream, and quickly carried to the brain.

The chances of overdosing and poisoning with crack are thus greatly increased.  The rapid ‘high’ rapidly subsides, leading to depression that needs to be relieved by taking more of the substance.

Such a cycle increases the chances of addiction and dependency.


Root of All Evil?

A cocaine grain stuck onto the fibres of a dollar bill, seen through a microscope.
Cashcoke: A cocaine grain seen stuck to one of the fibres on an American dollar bill

Now, for the roots of all evil: Drugs and Money.  A lethal combination.  But there is no way of escaping sin…

You see…

Cocaine hydrochloride is a very stable compound.  It binds closely to the ink in paper currency.  Hence most Americans handle cocaine every day of their lives.

As with poisons, the classification of drugs of abuse is helpful, notably in forensic science and medicine.  While one is more concerned with their legal status, the other looks at their chemical similarities.

As for money…  At least, cocaine has pharmaceutical uses.

Joking apart, cocaine is a very powerful and dangerous substance.  So, don’t play with it…  But if you’re going to, take it (and its associated physical ill-effects) very seriously… and stay safe.

Like playing poker, you can lose BIG.

Don’t go all-in!