Stimulants

                                     

                                 

Stimulants

• Stimulate nervous system• ↓tiredness, ↑ alertness, competitiveness and aggression• In competition - pain barrier?

– Danger in contact sports, pain reduction and in the heat

• In training - increase intensity of session• Evidence efficacy controversial

– Little evidence, 1-2 %, placebo effect?

• Why banned?

• 3 main banned stimulants– ephedrine, amphetamine and cocaine

How do stimulants work?

X

X

Blood

NerveTerminal

Receptors

(b)+

- +(a)(c)

BloodBrainbarrier

synapse

a) increase neurotransmitter release onto receptors (amphetamine, ephedrine, ecstasy)

b) directly stimulate post-synaptic receptors (ephedrine, caffeine)

c) inhibit neurotransmitter re-uptake (cocaine, amphetamine, prozac)Differing effects whether act via (a) or (c)

Amphetamines

• Controlled substances, appetite suppression, nasal decongestant, antidepressant

• Today - tx narcolepsy• Used by athletes to sharpen

reflexes, reduce tiredness, enhance mood, obscure pain from injuries

• Mechanism– Primarily enhances brain

activity of noradrenaline and dopamine

• Absorbed mainly sm intestine, [plasma] peaks 1-2 hrs post admin– Filtered by kidneys, detected in

urine for at least 48 hrs post admin

Amphetamines

• Performance effect may be small (1-2%) – dosage important• May:

– Improve reaction time when fatigued;– Increase muscular strength and endurance;– Increase acceleration;– Raise lactic acid levels at max exercise;– Loss body fat.

• Some evidence confidence• May increase ability to tolerate anaerobic exercise Wyndham et al.

(1971). Questions if any ergogenic effect.• Side effects

– Anxiety, judgment errors, irritability, dry mouth, tremors, insomnia, dependence (tolerance develops), depression following withdrawal, and death

‘Put me back on my bike’

Other sympathomimetics

• Ephedrine and methylephedrine ([> 10µg.ml-1] urine), pseudoephedrine (monitored list);

• Nutritional supplements• Natural CNS stimulants - species Ephedra• Less potent than amphetamines, but longer lasting• Enhances release of noradrenaline from

sympathetic neurones and stimulates α- and β- receptors– Increases hr, peripheral resistance & thus bp

(most dangerous side effect)

Other sympathomimetics

• Moderate bronchial smooth muscle relaxant– Cold cures

• Vasodilator for asthma but now linked with cardiac arrhythmia

• Side effects similar to amphetamines but milder– Interaction with NSAID - bp

• Joint use with caffeine – augments adverse CV and CNS effects.

Ephedrine in sport• Inconsistent, probably insignificant ergogenic

effect for power, endurance, strength or speed– Hodges et al., (2006) Pseudoephedrine enhanced

1500m performance (6s, 2%)• Studies in combination

– Caffeine + ephedrine – greater benefit than either drug on its own

– ↑performance submax steady state, short + long distance running, max & supramax cycling, wt lifting,

– Increases blood glucose and lactate, increased adrenaline and dopamine, hr, reduced RPE

– Nb. Caffeine and ephedra alkaloids no longer on banned list

• May become popular ergogenic aid• Dangerous?

• Magkos et al. (2004) MSSE 24(13):871-849

Cocaine• Ingredient of Vin Mariani used by Pope Leo XIII

– ‘wine for athletes’;• Ingredient in coca cola until 1903• Freud used to cure his own depression & noted

+ve effect on strength & reaction time;• Local anaesthetic, reduction in fatigue, euphoria

but replaced by dysphoria.• Highly addictive

Cocaine• Peak effect 5 – 15 mins (snorting), lasts up to 1 hr.

• Studies inconclusive – may only be effective in

short duration events of high intensity• Many instances of positive tests following

recreational use;• Distorts reality so may perceive enhanced

performance;• Paranoia, glycogenolysis (and increased [lactate]),

seizures, hypertension and myocardial toxicity arrhythmias and sudden death especially following intense exercise (deaths in athletes have been reported)

Caffeine

• Prior to 2004 on banned list with tolerance limit in urine (12 µg.ml-1)

• IOC removed from banned list 2004• Main natural sources – coffee (75%), tea,

cocoa, cola;• Readily absorbed, blood levels peak 60 min

post-ingestion. 2-10 hr ½ life. Degraded by liver, eliminated in urine and sweat (Kovacs et al., 1998)

Caffeine and Endurance Performance

• Caffeine ingested 1hr prior to exercise ↑ plasma [ffa] and ↑ performance (Costill et al., 1977; Essig et al., 1980; Ivy et al., 1979)

• However…– ↑ [ffa] without ↑ [ffa] oxidation (Knapik et al., 1983;

Tarnopolski et al., 1992)

– ↑[ffa] but no improvement in performance (Erikson et al., 1987; Powers et al., 1983; Tarnopolski et al., 1989)

– no effect on fat metabolism or performance (Bond et al., 1987; Toner et al., 1982; Winder et al., 1986)

Caffeine and Endurance Capacity

• Dose of 3 mg.kg-1 – 9 mg.kg-1 bm increased endurance capacity by 10-20% at ~85% VO2max– Costill et al., 1978, Graham et al., 1987; Graham &

Spriet, 1991; Pasman et al., 1995; Spriet et al., 1992;

• Also decreased RPE• May increase glucose uptake from gut (Yeo et al.,

2005)• Effects may depend on dosage, fitness level,

habitual consumption, type/duration of exercise

Caffeine and maximal exercise

• i.e. 100% VO2max – lasting 3-8 min• Some have found improved performance

– Falk et al., 1989; Sasaki et al., 1987; Jackman et al., 1996; Wiles et al., 1992.

– Latter found glycogen levels were not spared• Mech unknown

– Facilitated recruitment of muscle fibres?• Spriet (1995) suggests effect on muscle ion

handling, enhanced anaerobic energy production, or reduced RPE

Caffeine and supra-maximal exercise

• Effects unclear and ltd no studies

• Williams et al., (1988); Collomp et al., (1991) – both no effect on 15/30 s sprints;

• No effect on Wingate (Greer et al., 2006, Lorino et al., 2006)

Caffeine and cognitive functioning

• Caffeine ingested (2 - 3 mg.kg-1 bw) before/during 1hr of exhausting exercise

• Attention, psychomotor skills, memory improved afterwards (Hogervorst et al., 1999)

• Also possible improvement of concentration

Caffeine Dosage

• Pasman et al., (1995) no effect of doses > 5 mg.kg-

1 bm on ride to exhaustion;• Similar findings in runners – improvement with 3

and 6, but not 9 mg.kg-1 bm (Graham and Spriet, 1995)

• Kovacs et al., (1998) 2 or 3 mg.kg-1 bm. The higher dose improved performance more – dose of 4.5 mg.kg-1 bw did not improve further

• Effects found as low as 1.5 – 2.1 mg. .kg-1 bm (Kovacs et al., 1998, Cox et al., 2002)

Habitual Users?

• May have different metabolic response (blunted ffa release, catecholamine excretion at rest Dodd et al., (1991)– However no evidence of performance

difference;

• Withdrawal for 2-4 days – no effect (Van Soeren and Graham, 1998)

• Needs further study

Mechanisms

1. Caffeine increases lipolysis and spares muscle glycogen;

2. Adenosine receptor antagonism

Side effects

• Non-habitual users– GI distress, headache, tachycardia, restlessness,

irritability, tremor, high bp, premature LV contractions

• Diuretic in resting conditions (no effect during exercise due to adrenaline)

• V high doses – peptic ulcer, seizures, coma and †

Caffeine

• Comparison of 2004 to pre-removal caffeine (Van Thuyne and Delbeke (2006)– Levels have ↓ apart from cycling where % of

+ve samples have ↑– Also high in powerlifting (taken with ephedrine

and aspirin)

Refs

• Avois et al., (2006) Central nervous system stimulants and sport practice. Br J Sports Med 40(Supp 1):i16-i20

• Wyndham GH et al., (1971) Physiological effects of the amphetamines during exercise South Afr Med J 45: 247-52